Peritoneal Dialysis Systems, Devices, and Methods

ABSTRACT

A method of performing a peritoneal dialysis treatment includes connecting a disposable unit to a source of water. The disposable unit includes at least a first container holding a sterile concentrate containing an osmotic agent, a second container holding a sterile concentrate containing electrolytes, an empty sterile mixing container, and a tubing set with a pre-attached peritoneal fill/drain line. The method also includes receiving a prescription command by a controller, indicating at least the fill volume and desired final concentration of the osmotic agent to be used for a current fill cycle under said treatment, and pumping a quantity of the concentrated osmotic agent that is at least sufficient to achieve the desired final concentration into the mixing container. The contest of the mixing container are mixed, further diluted or concentrated, and then flowed to a patient.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 15/400,978 filed Jan. 7, 2017, which is a continuation of U.S.patent application Ser. No. 14/006,763 filed Oct. 2, 2013, which is anational stage entry of International Application No. PCT/US2012/030350filed Mar. 23, 2012, which claims the benefit of U.S. ProvisionalApplication Nos. 61/466,921 filed on Mar. 23, 2011; 61/490,183 filed May26, 2011; and 61/509,240 filed on Jul. 19, 2011.

BACKGROUND

The disclosed subject matter relates generally to the treatment of endstage renal failure and more specifically to devices, methods, systems,improvements, and components for performing peritoneal dialysis.

Peritoneal dialysis is a mature technology that has been in use for manyyears. It is one of two common forms of dialysis, the other beinghemodialysis, which uses an artificial membrane to directly cleanse theblood of a renal patient. Peritoneal dialysis employs the naturalmembrane of the peritoneum to permit the removal of excess water andtoxins from the blood.

In peritoneal dialysis, sterile peritoneal solution is infused into apatient's peritoneal cavity using a catheter that has been insertedthrough the abdominal wall. The solution remains in the peritonealcavity for a dwell period. Osmosis exchange with the patient's bloodoccurs across the peritoneal membrane, removing urea and other toxinsand excess water from the blood. Ions that need to be regulated are alsoexchanged across the membrane. The removal of excess water results in ahigher volume of fluid being removed from the patient than is infused.The net excess is called ultrafiltrate, and the process of removal iscalled ultrafiltration. After the dwell time, the dialysate is removedfrom the body cavity through the catheter.

Peritoneal dialysis requires the maintenance of strict sterility becauseof the high risk of peritoneal infection. The risk of infection isparticularly high due to the long periods of time that the patient isexposed to the dialysate.

In one form of peritoneal dialysis, an automated cycler is used toinfuse and drain dialysate. This form of treatment can be doneautomatically at night while the patient sleeps. One of the safetymechanisms for such a treatment is the monitoring by the cycler of thequantity of ultrafiltrate. The cycler performs this monitoring functionby measuring the amount of fluid infused and the amount removed tocompute the net fluid removal.

The treatment sequence usually begins with an initial drain cycle toempty the peritoneal cavity of spent dialysate, except on so-called “drydays” when the patient begins automated treatment without a peritoneumfilled with dialysate. The cycler then performs a series of fill, dwell,and drain cycles, typically finishing with a fill cycle.

The fill cycle presents a risk of over-pressurizing the peritonealcavity, which has a low tolerance for excess pressure. In traditionalperitoneal dialysis, a dialysate container is elevated to certain levelabove the patient's abdomen so that the fill pressure is determined bythe height difference. Automated systems sometimes employ pumps thatcannot generate a pressure beyond a certain level, but this system isnot foolproof since a fluid column height can arise due to apatient-cycler level difference and cause an overpressure. A reverseheight difference can also introduce an error in the fluid balancecalculation because of incomplete draining.

Modern cyclers may fill by regulating fill volume during each cycle. Thevolume may be entered into a controller based on a prescription. Theprescription, which also determines the composition of the dialysate,may be based upon the patient's size, weight, and other criteria. Due toerrors, prescriptions may be incorrect or imperfectly implementedresulting in a detriment to patient well-being and health.

Systems that measure pressure have been proposed. For example, apressure sensor in contact with a fluid circuit at the cycler has beendescribed. The sensor indicates the pressure at the proximal end of thefill/drain line. During operation, a controller connected to thepressure sensor changes the operation of the peritoneal dialysis machinein response to changes in pressure sensed by the pressure sensor.

SUMMARY

Briefly, an automated peritoneal dialysis system provides variousfeatures including prescription-driven dialysis fluid preparation, anintegrated disposable fluid circuit, and sensor capabilities that allowaccurate filing and draining control with high safety margins. Featuresinclude a peritoneal fluid circuit with a pressure sensor at either endand methods and devices for using the pressure signals. Other featuresand embodiments are disclosed.

Objects and advantages of embodiments of the disclosed subject matterwill become apparent from the following description when considered inconjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments will hereinafter be described in detail below with referenceto the accompanying drawings, wherein like reference numerals representlike elements. The accompanying drawings have not necessarily been drawnto scale. Where applicable, some features may not be illustrated toassist in the description of underlying features.

FIG. 1 shows a peritoneal dialysis system with pressure sensors locatedat a patient and at a peritoneal dialysis cycler, according toembodiments of the disclosed subject matter.

FIG. 2A shows a pod-type pressure sensor, according to embodiments ofthe disclosed subject matter.

FIG. 2B shows a peritoneal dialysis tubing set with an integratedpressure sensor according to embodiments of the disclosed subjectmatter.

FIG. 3A shows a cycler and peritoneal dialysis fill/drain line,according to embodiments of the disclosed subject matter.

FIG. 3B shows a fill/drain line with a peritoneal catheter according toembodiments of the disclosed subject matter.

FIGS. 4A and 4B show a fill/drain line with a peritoneal catheteraccording to further embodiments of the disclosed subject matter.

FIGS. 5A-5C show threads of a procedure for monitoring fill/drainprocesses of a cycler using pressure sensors according to embodiments ofthe disclosed subject matter.

FIG. 6A shows a peritoneal dialysis solution preparation and treatmentsystem according to embodiments of the disclosed subject matter.

FIG. 6B shows the peritoneal dialysis solution preparation and treatmentsystem of FIG. 6A in a first phase of fluid preparation in which osmoticagent is added to a batch container, according to embodiments of thedisclosed subject matter.

FIG. 6C shows the peritoneal dialysis solution preparation and treatmentsystem of FIG. 6A in a second phase of fluid preparation in which adialysate precursor is obtained by dilution and mixing the contents ofthe batch container, according to embodiments of the disclosed subjectmatter.

FIG. 6D shows the peritoneal dialysis solution preparation and treatmentsystem of FIG. 6A in a third phase of fluid preparation in which thedialysate precursor properties are verified, according to embodiments ofthe disclosed subject matter.

FIG. 6E shows the peritoneal dialysis solution preparation and treatmentsystem of FIG. 6A in a fourth phase of fluid preparation in whichdialysate precursor is further prepared by addition of electrolyte tothe batch container, according to embodiments of the disclosed subjectmatter.

FIG. 6F shows the peritoneal dialysis solution preparation and treatmentsystem of FIG. 6A in a fifth phase of fluid preparation in which end-usedialysis solution is prepared by adjustment of the dilution of the batchcontainer contents, according to embodiments of the disclosed subjectmatter.

FIG. 6G shows the peritoneal dialysis solution preparation and treatmentsystem of FIG. 6A in a sixth phase of fluid preparation in whichdialysis solution in the batch container is verified, according toembodiments of the disclosed subject matter.

FIG. 6H and FIG. 6K show the peritoneal dialysis solution preparationand treatment system of FIG. 6A in in various treatment modes, accordingto embodiments of the disclosed subject matter.

FIG. 7A shows a disposable for use with the peritoneal dialysis systemof FIG. 6A according to embodiments of the disclosed subject matter.

FIGS. 7B and 7C shows an embodiment of the disposable of FIG. 7A in useon a cycler and fluid preparation device according to embodiments of thedisclosed subject matter.

FIG. 8A shows a schematic diagram of a peritoneal dialysis system thatgenerates peritoneal dialysis solution from concentrate according toembodiments of the disclosed subject matter.

FIGS. 8B and 8C show how the valves of a manifold module operate toselectively block and permit the flow of fluid through the manifoldmodule.

FIG. 8D and 8E show fluid circuit embodiments.

FIG. 9 shows a schematic diagram of a water purifier and with featuresto support renal replacement therapy delivery systems according toembodiments of the disclosed subject matter.

FIG. 10 shows a schematic diagram of a peritoneal dialysis system thatuses pre-mixed dialysate according to embodiments of the disclosedsubject matter.

FIG. 11 shows a flow chart describing respective methods for preparing aperitoneal dialysis system for treatment and performing a treatmentusing either pre-mixed dialysate or concentrate.

FIG. 12 shows a method for fluid circuit priming which may be used inone of the processes shown in FIG. 11 according to embodiments of thedisclosed subject matter.

FIG. 13 shows a method for fluid preparation which may be used in one ofthe processes shown in FIG. 11 according to embodiments of the disclosedsubject matter.

FIG. 14 shows a method of pressure testing a sterile filter which may beused in one of the processes shown in FIG. 11 according to embodimentsof the disclosed subject.

FIG. 15 shows a method for priming a patient line leading to a patientaccess, which may be used in one of the processes shown in FIG. 11according to embodiments of the disclosed subject.

FIG. 16 shows a method for disconnecting and flushing a used fluidcircuit which may be used in one of the processes shown in FIG. 11according to embodiments of the disclosed subject.

FIGS. 17A-17H, 17J-17N, and 17P-17T illustrate steps of preparation for,and termination of, a treatment which may be used in one of theprocesses shown in FIG. 11 according to embodiments of the disclosedsubject.

FIG. 18 illustrates a control system according to embodiments of thedisclosed subject matter.

FIG. 19 shows a fluid path and actuator layout according to embodimentsof the disclosed subject matter.

DETAILED DESCRIPTION

Referring to FIG. 1, a peritoneal dialysis system 100 includes aperitoneal dialysis (PD) cycler 101 with an internal pump (not shown).The PD cycler 101 pumps dialysis solution from a container 106, such asa bag, or other source, to a patient access 114 through a fill/drainline 112 to a peritoneal catheter 114 into the peritoneum of a patient108. This happens during a fill cycle.

During a drain cycle, spent dialysate is withdrawn from the patient byflowing in reverse through the fill/drain line back to the cycler 101and out through a drain 104. The cycler 101 quantifies the volume offluid that is infused and drained and provides an accounting of thedifference to allow the net amount of fluid withdrawn from the patientto be determined.

The pump may be any suitable pump such as a diaphragm pump or aperistaltic pump. Alternatively, the cycler may rely on other fluidconveyance systems such as an over or under-pressurized supply/sumpcontainer, gravity feed or any other suitable mechanism.

A controller 116 allows the system to regulate a flow rate to ensure thepatient's peritoneal cavity is not over-pressurized. The flow regulationmay be accomplished by changing a speed of a pump or by means of avariable flow restrictor or any suitable mechanism conforming to therequirements of the type of fluid conveyance system employed.

Prior art systems have prevented exceeding a safe limit on peritonealpressure by a variety of mechanisms, including measuring pressure in thefill line using a pressure sensor located on the PD cycler and applyingfeedback control of the pump to ensure a limit is not exceeded. Anotherprior art device for preventing over-pressurization of the peritonealcavity limits the total head pressure by employing a gravitational feed.

An alternative may employ a pressure detection device 110 located at theend of a fill line 112, adjacent the patient 108, or at the access 114itself, to take pressure readings close to the patient. By usingpressure measurements from this location, the error in pressuremeasurement of the peritoneal cavity due to pressure loss in the fillline during filling of the cavity is eliminated. In this way the flowrate can be controlled by a continuous feedback loop to maintain thecavity pressure below a desired safety threshold. Locating the pressuresensor close to the patient also eliminates another source of errorwhich may arise from a level difference between the supply side of thefill line 112 and the catheter end of the fill line. That is, if thecycler 101 is located higher than the patient access, the gravitationalhead pressure of the fill line could cause a greater pressure thanindicated by a prior art pressure sensor located at the PD cycler whichmay not otherwise be accounted for, causing excessive pressure to beapplied. A low cycler may cause inadequate pressure and slow fillcycles.

In the embodiment of FIG. 1, to provide accurate pressure indication,the pressure detection device 110 is located close to the patient 108 tomaximize responsiveness to changes in the peritoneal cavity pressure andminimize the effect of pressure drop due to flow resistance. Anelectrical pressure transducer may be located at the end of the line.Alternatively, a pressure pod as described in the attached US patentpublication 20070179422 may be used. In an embodiment, a pressuretransducer may be located at the controller or cycler as shown in FIG. 1and also at the patient access to measure the pressure of the peritonealspace without the signal bias produced by line pressure drop in the line112.

FIG. 2A shows a pressure measurement pod 10. In the pod 10, air chamber45 is in communication with an air port 12 and air line 40 that can beconnected to a pressure transducer (not shown). Fluid flows through afluid chamber 60 between an inlet line 35 connected to an inlet port 70and out of the fluid chamber 60 through an outlet port 72 into an outletline 15. The pressure of the fluid in the fluid chamber 60 displaces adiaphragm 25 until the air chamber 45 and fluid chamber 60 are atequilibrium, which is preferably the situation when the air and fluidchambers 45 and 60 are at equal pressure.

The pod 10 is primarily made of two parts, a fluid-side shell 30 and anair-side shell 17, that, together, form an enclosure 5 that defines thefluid and air chambers 60 and 45. The ratio of the minimum to themaximum volume of the air chamber 45, including the volume of the line40 and port 12, is proportional to the total pressure variation that canbe measured by the transducer attached to the line 40.

Referring now to FIG. 3A, a fill/drain tubing set 309 has a pod 304 forindicating pressure. The pod 304 may conform to the design of pod 10 ofFIG. 2A and may be used to provide a pressure indication at a distal endof a fill/drain line 306. FIG. 3A shows a PD cycler 318 with source ofdialysate 320 and connectors 316 and 314 for the fill/drain line and apressure sensing line 302, respectively. The pressure sensing line 302connects a pressure transducer (not shown separately) on the PD cycler318 to the pod 304 to permit the transducer to read the pressure exertedon the diaphragm (not shown in FIG. 3A) of the pod 304. The pod 304 isconnected directly to the fill/drain line 306 in an inline configurationand close to an access connector 326 to which a peritoneal catheter 322can be connected by connector 324. The pressure sensing line 302 isattached to the fill/drain line 306, for example by a series ofconnectors 308, so that it runs parallel along the fill/drain line 306.The PD cycler 318 may also be provided with an additional pressuresensing device forming part of a fluid circuit to which the fill/drainline 306 is attached and configured to measure the pressure in thefill/drain line 306 close to the PD cycler 318.

Thus, in the present embodiments, the pressures at each end of thefill/drain line 306 may be determined by a controller that operates thecycler at all times during operation of the PD cycler 318 and applied ascontinuous input signals to the controller during fill and drainoperations. As discussed below, these inputs can be used to allow thecapture and storage of vital signs, detection of flow restrictions andkinks in the fill/drain line 306, and allow the regulation of flow ratewhile managing the pressure within the peritoneum.

FIG. 2B shows a peritoneal dialysis tubing set 60 with an integratedpressure sensor 45 located at a distal end of a fill-drain line 47. Thefill-drain line may have one or two lumens for shared or separate filland drain use, respectively. A pressure transducer 45 is in pressurecommunication with a lumen of the fill-drain line 47. If there areseparate fill and drain lumens, each may carry its own pressuretransducer 45 or only one, for example, the fill line, may carry apressure transducer 45. The transducer may be, for example, a straingauge component that reacts to isotropic pressure (e.g. fully wetted andimmersed) or it may be a strain gauge component built into the wall ofan inline fluid conveying component. Other configurations are alsopossible to achieve the effect of providing pressure sensing at thedistal end of the fill-drain line 47. A pair (or more, as necessary) ofconductors 48 run along the length of the fill-drain line 47 to connectto an electrical connector 50 which connects to a driver circuit 51. Thedriver circuit may contain a power supply and reader circuit or othersuitable circuitry for generating a pressure signal from the pressureapplied by fluid in the lumen of the fill-drain line 47 at its distalend. A connector 46 configured for connection to a peritoneal catheteris attached to the distal end and a connector 49 for connection to asource and/or sink of fluid is located on the proximal end of thefill-drain line 47. The connector 46 may be permanently attached to aperitoneal catheter or may have a peritoneal catheter preinstalledthereat. The connectors 49 and 46 may be sealed to isolate the lumen andthe unit 60 delivered as a sealed unit with a sterile lumen.

Referring now to FIG. 3B, a variation of a fill/drain line tubing set330 similar to the embodiment 309 of FIG. 3A has a double tube 332 withfill/drain line portion 332A having a large diameter lumen on one sideand pressure line portion 332B having a small diameter lumen 332B on theother side. Both lumens run the entire length of the fill/drain tubingset 330. Connectors 334 and 336 are provided at proximal end forconnecting the fill/drain line side 332A lumen and the pressure lineside 332B lumen to a fluid circuit and pressure sensor respectively. Apressure pod 331 is connected to convey pressure signals through thesmall lumen of the pressure line side 332B. The pressure pod 331 isconnected inline with the fill/drain lumen such that pressure is appliedto an internal diaphragm indicating pressure at the distal end of thefill/drain lumen. Note that the fill/drain tubing set 330 may be formedin various ways, for example by welding two tubes together or byextruding the two tubes with an integral web between them. Matingconnectors 326 and 324 may be provided for connecting a peritonealcatheter 322.

The embodiment of FIG. 3B may be used in the same manner as that of FIG.3A. Thus, in this embodiment also, the pressures at each end of thefill/drain line may be determined by a controller that operates thecycler at all times during operation of any suitable PD cycler andapplied as continuous input signals to the controller during fill anddrain operations.

Referring now to FIGS. 4A and 4B, a peritoneal catheter 350 has anintegrated pressure transducer 342 which is connected by embeddedelectrical leads 340 running along the catheter 350 to a terminalconnector 340. A pair of cuffs 344 is located on a proximal section 348near the proximal end which is provided with a fluid connector 352. Thepressure transducer 342 may be a strain gauge device with a flexiblehermetic wrapper that can be welded to the catheter or integrally moldedin. The connector 366 may be of any suitable type and may be connected alead 365 carried on a fill/drain tubing set 360 similar in design tothat of FIG. 3A (or that of FIG. 3B or any other suitable design). Thelead 365 may have suitable mating electrical connectors for connectionto a cycler with a controller to apply a pressure signal from thetransducer 342. The catheter 350 has openings to distribute outflow andsuction in the peritoneal cavity as in known catheters for peritonealdialysis.

A variation of any of the foregoing embodiments may be fill/drain lineswith separated fill and drain lines, each having a respective lumen. Thelines may be connected to the cycler by separate attachments, merged bya T or Y junction at the cycler, merged at the peritoneal catheter or acombination of these.

Referring now to FIGS. 5A to 5C, an example process for monitoringpressure signals from the foregoing peritoneal devices is now described.FIG. 5A shows a process for storing a string of pressure signal samplesfor an interval of time. For example, the pressure signal may be sampledat 100 ms intervals for a period of 20 seconds at S12 and the processrepeated after a delay S10. The samples may be stored in a memory formany samples covering an entire treatment or for only a portion of atreatment. Alternatively to the process of FIG. 5A, pressure datasamples respective of each pressure sensor may be continuously stored ina memory and refreshed after archiving following a treatment orrefreshed in a first-in first-out fashion according to a time intervalso as to preserve only a short term historical record. In anotheralternative, only instantaneous pressure data may be stored.

The procedure of FIG. 5B derives various information from the datastored by the operation of FIG. 5A. The operation may be applied to eachpressure signal, including, for example, those provided by a distalpressure sensor (e.g., 110 of FIG. 1) and a proximal pressure sensor(e.g., 102 of FIG. 1). The procedure of FIG. 5A recovers the storedsignal segment S22 and processes it to remove noise S24 (e.g. low passfiltering, smoothing, thresholding or other suitable filtering process).At S26, the pressure signal segment is analyzed to generate areliability metric indicating its accuracy. The latter may be done invarious ways, for example, by identifying differences between a storedactual reading and a measured pressure or rate of change in pressure. Inaddition, or alternatively, the goodness of fit of the pressure profileto a stored model may provide a measure of accuracy (the curves beingfitted in S28). The pressure reading may be compared to a profile. InS28, pressure profile data is translated into a respiration rate andpulse rate by fitting expected respiration and pulse curves to thestored data and the reliability metric and analyzing.

More sophisticated analysis may be done in S28 as well, for example, byfitting the measured data curves to curves that characterizeidentifiable conditions, such as dangerous conditions. For example, aleak may be indicated by a sharp drop in pressure at the distal locationalong with a gradual trend of ebbing pressure. The profile templatesthat characterize events may be may be determined via experiment ormodeling or simply by judgment and stored in a memory of the controller.Other events that may be identified, for example by comparing distal andproximal pressure readings, are kinks or flow restrictions in thefill/drain line or changes in the properties of fluid, for example suchas may evidence peritoneal infection. The latter may be detected byidentifying an excessive pressure drop in the fill/drain line during adrain operation, which may be caused by excessive viscosity in the spentdialysate.

In S30, events detected in the profile data, current pressure values,historical data, and reliability estimates are updated. Current data,for example, may be stored in a location representing current values andhistorical data may be stored in memory locations representinghistorical values along with time and date values. For example, a memorylocation may hold a current estimate of patency of the fill/drain line.The event detection results may be represented as status flags andassociated reliability estimates or other metrics such as a measure ofgoodness of fit to a characteristic curve or instantaneous value.

Referring to FIG. 5C, during a fill or drain cycle S42, the eventrecognition status and/or instantaneous values, such as those ofpressure, are read by the controller from the controller memory S44 andcompared to various threshold levels S46, S48, S50 and if the thresholdtest is met, an alarm indication may be generated S52 and the cycler maybe placed in a safe mode corresponding to the detected event orcondition. Otherwise, control may return to S42.

Archived data may be transferred to a data store for combination withdata of multiple patients, for example via an internet connection, foranalysis and comparison purposes.

The conditions detected in S46, S48, S50 may include, for example:

-   -   1. A reduction in the strength of vital signs (e.g.,        respiration, pulse) signal evidencing a line obstruction, loss        of patency of the catheter or other problem;    -   2. Excessive pressure loss for an instantaneous flow rate, which        may indicate a line obstruction, kink, or pinching of the line        or other problem;    -   3. Excessive pressure of the peritoneum which may be compensated        by reducing or stopping the flow rate;    -   4. Excessive drain flow pressure loss in the drain line due to        high viscosity which may indicate an infection.

Referring now to FIG. 6A, a peritoneal cycler system 600 generatescustom peritoneal dialysis solution according to a prescription storedin a controller 610. The prescription may be entered in the controllervia a user interface 601, via a remote terminal and/or server 603 or byother means such as a smart card or bar code reader (not shown). Thecontroller applies control signals to a fluid conveyer and circuitswitch 616 and a water purifier 620 and receives signals from distal andproximal pressure sensors 613 and 614, respectively, on a fill/drainline 650 which may be in accord with foregoing embodiments.

The fluid conveyor and circuit switch 616 is a fluid circuit elementwith one or more sensors, actuators, and/or pumps which is effective toconvey fluid between selected lines 642, 644, 646, 648, 650 and 618responsively to control signals from the controller 610. Exampleembodiments are described herein, but many details are known from theprior art for making such a device so it is not elaborated here.

A multiple-container unit 641 includes a pre-filled, pre-sterilizedosmotic agent container for osmotic agent concentrate 602 and anotherelectrolyte container with electrolyte concentrate 604. The unit 641also contains an empty batch container 606 which is large enough to holda sufficient volume of dialysis solution for the completion of at leastone fill cycle of an automated peritoneal dialysis treatment. Thecontainers 602, 604, and 606 may be flexible bag-type containers thatcollapse when fluid is drawn from them and therefore, do not require anymeans to vent air into them when drained.

Osmotic agent container 602, electrolyte container 604, and batchcontainer 606 are all connected by respective lines 642, 648, 644, and646 to the fluid conveyor and circuit switch 616. The fill/drain line(or multiple lines) 650 and a spent fluid drain line 618 with aconductivity sensor 628 may also be connected to the fluid conveyor andcircuit switch 616. The fluid conveyor and circuit switch 616 also has afill line 631 for receiving water. The water purifier 620 may be apurifier or any source of sterile and pure water including apresterilized container of water or multiple containers. In a preferredconfiguration, water purifier 620 may be configured as described inWO2007/118235 (PCT/US2007/066251) hereby incorporated by reference inits entirety and attached to the provisional application. For example,the water purifier 620 may include the flow circuit components of FIG.22 including the water purification stages and conform generally to themechanical packaging design shown in FIG. 24 of the incorporated(attached) publication.

FIG. 6B shows a preliminary stage of fluid preparation prior totreatment according to an embodiment of the disclosed subject matter.The controller 610 reads a prescription and generates a command,responsive to a treatment preparation initiation command, to flowosmotic agent concentrate from container 602 to the batch container 606.The command is applied to the fluid conveyor and circuit switch 616 toconnect the osmotic agent concentrate line 642 to the batch fill line644 and also to convey the osmotic agent concentrate into the batchcontainer 606. This may be done by one or more valve actuators and oneor more pumps that form the fluid conveyor and circuit switch 616. Thefluid conveyor and circuit switch 616 may be configured to meter thequantity of osmotic agent precisely according to a predicted amount ofdilution by electrolyte and water to achieve the prescription. Themetering may be performed by a positive displacement pump internal tothe fluid conveyor and circuit switch 616 or other means such as ameasurement of the weight of the osmotic agent container 602 or thebatch container or a volumetric flow measurement device.

In an alternative embodiment, part of the water (less than the totalused for dilution as discussed below with reference to FIG. 6C) is addedto the batch container first, before the osmotic agent and electrolytes(if needed) are pumped into the batch container.

Referring now to FIG. 6C, a dilution stage is performed using theperitoneal cycler system 600. The controller 610, in response to theprescription, generates a command, to flow purified water from the waterpurifier 620 to the batch container 606. The command is applied to thefluid conveyor and circuit switch 616 to connect the purified water line631 to the batch container 606 to add a measured quantity of water todilute the osmotic agent concentrate in the batch container 606. Thecontroller may control the fluid conveyor and circuit switch 616 toensure the correct amount of water is conveyed. Alternatively, the waterpurifier may incorporate a flow measurement device or metering pump orother suitable mechanism to convey the correct amount of water. Thecontroller 610 may be connected to the water purifier 620 to effectuatethe dilution result. The fluid conveyor and circuit switch 616 may alsobe configured to circulate diluted osmotic agent solution through lines644 and 646 either simultaneously with the dilution or after thediluting water has been transferred to the batch container according toalternative embodiments.

The relative amounts of water, osmotic agent, and electrolyte may bedefined based on the ratiometric proportioning properties of the pump.Since a single tube is used to convey all the liquids into the batchcontainer, most sources of offset from predicted pumping rate (based onshaft rotations, for example) to actual pumping rate affect all thefluids roughly equally.

Referring now to FIG. 6D, the diluted osmotic agent solution in thebatch container 606 is tested to ensure the correct concentration ofosmotic agent is achieved. In an embodiment, the osmotic agentconcentrate 602 has an amount of electrolyte concentrate to generate aconductivity signal using the conductivity sensor 628 when fluid fromthe batch container 606 is conveyed by the fluid conveyor and circuitswitch 616 to the drain line 618 past the conductivity sensor. Theamount of electrolyte pre-mixed with the osmotic agent may be lowestratio of electrolyte to osmotic agent a possible prescription mayrequire. The fluid conveyor and circuit switch 616 may perform thefunction using one or more valve actuators and one or more pumps thatform the fluid conveyor and circuit switch 616. The fluid conveyor andcircuit switch 616 may be configured to meter the quantity of waterprecisely or the function may be provided by the water purifier 620. Thecontroller may add additional water or osmotic agent and test theconductivity again if the measured concentration of osmoticagent/electrolyte is incorrect. In addition to using a combined osmoticagent and electrolyte concentrate in osmotic agent container 602, in analternative embodiment, the osmotic agent container 606 holds osmoticagent concentrate with no electrolyte and osmotic agent concentration ismeasured directly by other means such as specific gravity (hydrometer),refractive index (refractometer), polarization, infrared absorption orother spectrographic technique.

FIG. 6E shows an electrolyte addition stage of fluid preparation priorto treatment according to an embodiment of the disclosed subject matter.The controller 610 reads a prescription and generates a command to flowelectrolyte from container 604 to the batch container 606. The commandis applied to the fluid conveyor and circuit switch 616 to connect theelectrolyte concentrate line 648 to the batch fill line 644 and also toconvey the electrolyte concentrate into the batch container 606. Thismay be done by one or more valve actuators and one or more pumps thatform the fluid conveyor and circuit switch 616. The fluid conveyor andcircuit switch 616 may be configured to meter the quantity ofelectrolyte precisely according to a predicted amount of dilution byosmotic agent and water that has been previously determined to be in thebatch container 606, to achieve the prescription. The metering may beperformed by a positive displacement pump internal to the fluid conveyorand circuit switch 616 or other means such as a measurement of theweight of the electrolyte container 604 or the batch container 606 or avolumetric flow measurement device.

Referring now to FIG. 6F, the electrolyte may be mixed using the batchfill and drain lines 646 and 644 in a closed loop. If necessary,depending on how much dilution was performed during the osmotic agentdilution process, further dilution may be performed as described above.The final formulation may be achieved by the process illustrated in FIG.6F. Then, as illustrated in FIG. 6G, the final electrolyte concentrationof the mixture in batch container 60 may be determined with aconductivity sensor 628 by flowing a sample therethrough.

In addition to mass or conductance measurements, other types of measuresmay be used to measure proportions of dialysis fluid components anddilution. For example, tracer chemicals such as radioactive tracers ordyes may be used.

Although gravimetric and tracer/conductance sensing were described asdevices for ensuring proper proportioning and dilution rates forachieving target prescriptions, it should be clear that the system mayemploy ratiometric proportioning as well, particularly where positivedisplacement pumping is employed. Ratiometric proportioning takesadvantage of the volumetric repeatability and predictability of certainpumps. For example, a particular pump can deliver a highly repeatablevolume of fluid for a given number of pumping cycles (pump rotations fora peristaltic pump or cycles for a diaphragm pump, for example). If alldialysis solution components (water, osmotic agent concentrate, andelectrolyte concentrate, for example) are delivered to the mixingcontainer using the same pump, including, for example, the pumping tubesegment of a peristaltic pump, then the volume ratios of the componentswill, after adjustment for potential flow path and/or viscositydifferences as described below, be fully determined by the number ofpump cycles used to convey each component.

This proportioning may supplement or substitute for measurement of thefluid conductance or density or other measurements. To convert thenumber of pump cycles to actual displaced mass or volume, a calibrationmay be performed and/or flow path (including fluid properties)compensation parameters may be employed. The flow path compensationparameters may be respective to each particular fluid flow path and/orfluid type, or may be identical for all fluid paths and fluid types. Toprovide enhanced accuracy, one or more pump calibration and/or flow pathcompensation parameters may be generated through a calibrationprocedure. Typically, flow path compensation factors will be establishedduring the development of the system and stored in non-volatile memory.Typically, one or more flow path calibration procedures will beperformed when the system is used by a patient. The calibrationprocedure may be performed after each new fluid set is installed, orbefore each batch preparation cycle, or even multiple times during thepreparation of a single batch. A disposable fluid set may be installedevery day. The calibration procedure may be done using water. Thecalibration may sequentially pump fluid through one or more of thefollowing stages:

From To Water source Drain Batch container Drain Osmotic agentconcentrate Drain container Electrolyte concentrate Drain containerPatient access Drain Batch container Patient access Osmotic agentconcentrate Batch container container Electrolyte concentrate Batchcontainer container Water source Batch containerIn the calibration procedure, fluid is pumped between any or all of thepaths identified above. A separate calibration coefficient may begenerated for each of the paths. The calibration coefficient may bestored in a memory or non-volatile data store, for example, as aparameter representing the number of ml/per pump rotation (or diaphragmpump cycle), or as a proportionality ratio relative to a particularreference flow path. The actual fluid quantity transported during thecalibration step may be measured by any suitable device (flow sensor)including volume or mass measurement devices or direct flow ratemeasurement with integration, for example, using laser Dopplervelocimetry, thermal transit time, magnetohydrodynamics, propellerhydrometer, positive displacement flow measurement, differentialpressure through a resistance such as a venturi, nozzle, orifice plate,or other flow obstruction, variable area or rotameter, pitot or impacttube, vortex shedding frequency counting, ultrasonic, or other device.Any of the disclosed embodiments may employ a flow sensor in which atleast the portion of which that carries fluid is disposable so that theflow rate (or total displaced fluid quantity) can be input to acontroller while allowing the use of a disposable fluid circuit.Examples include an ultrasonic soft tube flowmeter made by StrainMeasurement Devices SMD that non-invasively measures flow in soft tubingby means of slotted transducers in which a length of tubing can beinserted during fluid circuit installation. For cartridge embodiments,the PD cycler can employ a moving transducer stage that engages anexposed tube length of the cartridge after passive insertion of thecartridge.

The pumping system may also be sufficiently repeatable in a way thatallows precise ratios to be established without calibration, dependingon the predefined tolerances chosen by the system designer. If themanufacturing tolerances, including materials, are sufficientlycontrolled, a desired level of control over ratios may be achievedwithout in situ (point of care) calibration. A particularly sensitivecomponent in terms of guaranteeing repeatability is the pumping tubesegment of a peristaltic pump. In a first embodiment, the peristalticpump tube segment is made from a material whose mechanical and materialtolerances are controlled within predefined limits. The lengths of thetubing circuit elements and mechanical parameters are also controlledwithin respective predefined limits. A calibration may then be doneoutside the treatment context, e.g., in the laboratory, to calculateprecise values to convert pump cycles to fluid quantity transferred fora single lot of replaceable fluid circuits. The calibration may be donefor multiple lots. The calibration may also be done for each fluidcircuit. The calibration may also be done by the treatment system foreach fluid circuit. The calibration may also be done for each batch offluid prepared by the fluid circuit.

Referring to FIG. 6H, subsequent to the preparation of the contents ofthe batch container 606 as described above, the fluid conveyor andcircuit switch 616 may be configured to drain the patient 611 dependingon the patient's prior status. Spent dialysate fluid may be withdrawn bythe fluid conveyor and circuit switch 616 and conveyed through the drainline 618. Then, the contents of the batch container 606 may be conveyedas illustrated in FIG. 6K to the patient. Here the controller 610 hasconfigured the fluid conveyor and circuit switch 616 to flow fluid to apatient 612.

Referring now to FIG. 7A, a fluid circuit embodiment for implementingthe embodiment of FIG. 6A includes a disposable fluid circuit 700. Thefluid circuit 700 may include pre-attached osmotic agent and electrolyteconcentrate containers 760 and 762. Also, the fluid circuit 700 mayinclude pre-attached batch container 764. The contents of the osmoticagent and electrolyte concentrate containers 760 and 762 may besufficient for multiple cycles and thereby cover a complete automatedperitoneal dialysis treatment. The internal volume of the batchcontainer may be sufficient for one cycle or multiple cycles in a singleautomated peritoneal dialysis treatment.

The fluid circuit 700 is preferably a disposable unit that has acompletely sealed internal volume except for a water inlet connection730 for connection to a source of purified water, a drain connection713, and a connection for a patient access 717. The connectors 730, 713,and 717 may be sealed with a removable connector cap and the entiredisposable fluid circuit 700 sterilized as a unit. The water inlet line726 may include a sterile barrier 728 in the form of a sterile filter,for example, one with a pore size of 0.2 microns or smaller to filterout contaminants. Effectively, that leaves only the patient accessconnection 717 and the drain connection 713 as possible entry paths forcontaminants. However, the drain line 712 can incorporate a check valveto prevent inflow of fluids therethrough. It is generally a one-way pathas well, so this removes all but the patient access connection 717 as apossible route for contaminants to flow into the sealed volume of thefluid circuit 700.

The fluid circuit 700 includes fluid circuit manifold panels 702 and 704which each distribute flow along their respective lengths effectivelyallowing flow between any of the connected respective lines. Forexample, fluid from the osmotic agent line 724 can flow into themanifold 702 and be pumped through a pump line 706, which is configuredto mate with a peristaltic pump, into the manifold 704 and then into aselected one or more of the mixing line 715, drain line 714, and/orfill/drain line 716. The fluid circuit manifolds 702 and 704 may includesensor regions (not indicated).

A variety of alternative manifold and/or actuation devices can be usedto implement the methods described herein. For example, referring toFIG. 8D, a fluid cartridge 800 has two shell parts 802 and 803 thatpartially enclose a tubing set with manifold branches 806 (typ.) thatstem from manifold parts 812A and 812B. Windows 810, 805 in each shellpart 802 and 803 appear in pairs on either side of a branch 806 topermit a linear actuator (solenoid clamp, stepper and screw drive,pinching mechanism like a plier grip, or other kind of mechanism) toaccess, and selectively clamp, the segment 816 from outside the shell.

The shell housing is assembled as indicated by the dotted arrows into apartial enclosure. Alternatively the tubing parts and manifold may beattached to a single backplane or inserted in a support on a permanentmounting fixture of a PD cycler.

A window, provided by openings 804 and 815, similarly provides access toa pump tubing segment 816 by a peristaltic pump rotor. The pump tubingsegment 816 may be flanked by, and also be size-matched to connectedtubing, by pressure pods 814. Pressure pods for fluid pressuremeasurement are known in the art and the details are not providedherein.

The manifolds of the foregoing figures can be realized using a varietyof structures. For example, fluid circuit part 826 uses Y-junctions 828and connecting segments 827 to interconnect tubing branches 828. Thisstructure may be used in place of manifold part 812B, for example, and avariation for manifold part 812A.

The completed device 800 may form a fluid cartridge that can inserted ina cycler housing like a slice of bread in toaster or may be attached tothe actuators in other ways.

Actuator regions 732A-732H allow the selective closing of connections toa respective line such as drain line 716. This allows any of the linesconnected to manifold 702 to be connected to a line of manifold 704through the pumping line 706 by closing all the other lines except theselected lines. In manifold 704, actuator region 732A controls access topatient access line 716. Actuator region 732B controls access to drainline 714. Actuator region 732C controls access to mixing line 715. Inmanifold 702, actuator region 732D controls access to batch fill line718. Actuator region 732E controls access to drain line 718. Actuatorregion 732F controls access to electrolyte fill line 722. Actuatorregion 732G controls access to osmotic agent fill line 724. Actuatorregion 732H controls access to the water fill line 726.

The patient access line may include a pressure sensor 735 such as apressure pod as described above with an air line 734 and a connector 736for connection to a pressure transducer on a peritoneal dialysis cycleror, alternatively, to a sensor region on the fluid circuit manifold.

Referring now to FIG. 7B, a combined fluid preparation apparatus and PDcycler 788 is combined with a water purifier 790 forming a PD system701. A disposable fluid circuit unit 758 conforms to the generaldescription of the embodiment 700 of FIG. 7A. An automated peritonealdialysis cycler 788 has a control panel 776 and is configured to use thedisposable fluid circuit 758. Various actuators and sensors (e.g.,pressure transducers, temperature sensors, optical leak detectors, etc.are generally indicated at 772. A hatch 773 may be closed over thedisposable unit cassette 758 to bring the components thereof intoengagement with the various actuators and sensors 772.

The disposable fluid circuit unit 758 has a cassette portion 766 thatincorporates manifolds 762 and 764 (corresponding respectively tomanifolds 702 and 704 of FIG. 7A). The manifolds 762 and 764 areattached to each other but have internal flow areas that are not influid communication (isolated from each other) so that only a pump line768 allows fluid communication between the manifolds 762 and 764. Theother elements of the fluid circuit 758 are as described with referenceto FIG. 7A. The automated peritoneal dialysis cycler 788 is shown setatop a water purifier 790. The automated peritoneal dialysis cycler 788may include a tray 780 for supporting the batch container 764 and/or ascale 778 for measuring its weight. A support 782 supports the osmoticagent and electrolyte containers 760 and 762, respectively.

A registration area 770 (for example a recess area) of the automatedperitoneal dialysis cycler 788 has a peristaltic pump actuator 774. Theregistration area receives the cassette portion 766 of the disposablefluid circuit unit 758 as shown in FIG. 7C so that the pump line 768engages the peristaltic pump actuator 774 and the sensor and actuatorareas of the cassette engage the corresponding sensors and actuators 772of the automated peritoneal dialysis cycler 788.

Referring now to FIGS. 8A and 9, schematic diagrams of a peritonealdialysis system 900 and water purification system 901 are shown whichoperate together as a complete system as described in the presentspecification. The peritoneal dialysis system 900 includes a fluidmanagement set 900A. The fluid management set 900A is coupled to a fluidcircuit of the water purification system 901 which contains a permanentmodule 952 and consumable components including filter media and tubingsets 901A. The peritoneal dialysis system 900 includes a PD cycler anddialysate preparation module 949 which contains controls and much of thepermanent hardware; the water purification system may be interconnectedto share controls so that a single user interface panel 906 may be usedto control both for administration of treatment.

The PD cycler and dialysate preparation module 949 has a controller 907with a user interface panel 906. The user interface panel has controls906A, 906B, 906C and a display 906D. The controls and other features ofthe user interface panel 906 may include an audio output device, LEDlamps, touchscreen input, and other devices that may be employed forinteracting with digital electronic control systems. Preferably the userinterface panel 906 controls 906A, 906B, 906C are a small set of clearlydifferentiated controls that are color coded and shape-differentiated.

The fluid management set 900A includes disposable batch, electrolyte,and osmotic agent concentrate containers 908, 910, and 912, for example,bags that are connected to respective dialysis solution, electrolyte,and osmotic agent draw lines 916, 915, 914. The batch container 908 ispreferably an empty presterilized flexible container that is deliveredempty of air or fluid and permanently attached to the dialysis solutiondraw line and a batch fill line 917, the batch fill line 917 being usedto add fluid to the bag and the dialysis solution draw line 916 beingused to draw contents from the bag. Electrolyte and osmotic agentconcentrate containers 910 and 912 store, respectively, electrolyte andosmotic agent concentrate and are also permanently attached to osmoticagent and electrolyte draw lines 914 and 915. The containers and linesare preattached and provided in a sterile condition. The batch container908 is eventually filled with a mix of sterile water, osmotic agent andelectrolytes to form a dialysis solution prescription. The batchcontainer 908 has two lines while the other containers have a singleline. The osmotic agent and electrolyte containers 912 and 910 may befitted with non-reopening clamps 953.

The batch container 908 may be configured to accommodate sufficientdialysis solution for a single peritoneal dialysis fill cycle or it maybe large enough for multiple fill cycles. Thus a preparation cycle maygenerate enough dialysate for a complete treatment (for example anocturnal treatment cycle including multiple drain-fill cycles).

The batch, electrolyte concentrate, and osmotic agent concentratecontainers 908, 910, and 912 may rest on a heater and/or scale 902indicated by dashed lines. Temperature sensors 904 and 905 may beprovided on the surface of the heater and/or scale 902 to providetemperature signals to the controller 907, which controls the heaterand/or scale 902. The controller may be configured to warm the dialysatein the batch container 908, which rests directly on the heater and/orscale 902. The temperature sensors 904 and 905 may be positioned toensure the batch container 908 rests directly on the temperature sensors904 and 905. The combination of free convection in the large batchcontainer 908 (multiple liters), thin wall of the batch container 908,and the compliance of the wall help to ensure a reading of thetemperature sensors 904 and 905 that reflects the temperature of thecontents of the batch container 908. Note while the temperature sensors904 and 905 are shown positioned remote from the batch, electrolyte, andosmotic agent containers 908, 910, 912, it is intended that they belocated immediately adjacent to the batch container 908.

The draw lines 914, 915, and 916 and the fill line 917 connect to amanifold module 911 with two valve headers 941 and 946, separated by abarrier section 842, and interconnected by a pump tubing segment 944.The flow between the valve headers 941 and 946 occurs only through thepump segment 944 or through an external connection between the lineslinked to it, such as by flowing through the batch container 908 via thevalve headers 941 and 946 draw and fill lines 916 and 917. The manifoldmodule 911 in combination with a peristaltic pump actuator 943 and valveactuators 929, 930, 928, 931, 932, 933, 934, and 935 provides andregulates the flow of fluid between selected pairs of the tubing lines914, 915, and 916, the fill line 917, drain lines 920A and 920B, productwater line 919 and a patient line 945. The manifold module 911 also hassensor regions 936 and respective pressure transducers 924 and 925 togenerate pressure signals reflecting pressure on either side of the pumptubing segment 944.

The manifold module 911 also has chambers 913A and 913B and respectivepressure transducers 926 and 927 to generate pressure signals reflectingpressure on proximal and distal ends of the patient line 945. Thepressure chamber 913B is connected to a pneumatic signal line 909 whichis in turn connected to a pressure pod 951 configured to transmit thepressure in the patient line 945 distal end through the pneumatic signalline 909 to the chamber 913B. Chamber 913A is in communication with theend of the patient line 945 that is closest to it and conveys thepressure to the transducer 926 to generate a signal representing thepressure at the proximal end of the patient line 945. The controller 907is connected to control the peristaltic pump actuator 943 and valveactuators 929, 930, 928, 931, 932, 933, 934, and 935 and receivepressure signals from the pressure transducers 924 through 927. Themanifold module 911 may be pressed against the valve actuators 929, 930,928, 931, 932, 933, 934, and 935 by means of a door 973 which may have ahinge and latch as shown in the figures.

An alternative embodiment has a direct pressure-to-electrical transducerin place of the pressure pod 951, which obviates the need in suchembodiment for chamber 913B. A direct pressure-to-electrical transducermay take the form of an immersible strain gauge which is bulk-modedeformable so as to provide negative and positive pressure values oreither one as required. An electrical lead or wireless channel mayconvey a pressure signal to the controller 907. Such a transducer may beintegrated into a connector for the patient access. Alternatively, thedirect pressure-to-electrical transducer may be a pressure catheter,such as one integrated with the peritoneal catheter, as describedelsewhere in the present document.

The manifold module 911 has respective box shaped valve headers 941 and946. Each header has a plurality of valve structures that is actuated bya respective one of the valve actuators 929, 930, 928, 931, 932, 933,934, and 935. The valve actuators 929, 930, 928, 931, 932, 933, 934, and935 may be solenoid hammers, linear motors, pneumatic hammers or anysuitable device for applying a force to press on a respective one of theheader valves (one of the valves being indicated at 140). Referring toFIGS. 8B and 8C, a valve 140 is shown in an open position (FIG. 8B) anda closed position FIG. 8C). The plunger 136 of an actuator (such as 929)moves vertically to exert a force on a membrane 134 to close it over anopening 132. A tube 131 is attached by bonding to the header wall 135using a conforming port 133 to allow the tube 131 to be received andsealed to the header wall 135. The tube 131 is sealed to the header wall135 preventing flow between a lumen of the tube when the membrane isclosed over the opening 132. An interior volume 130 of the valve header941 or 946 is thereby only accessible selectively by operating theactuator to drive the plunger 13 accordingly. By selecting a pair ofactuators to open, flow can occur through the interior volume of thevalve header between the lumens of two tubes corresponding to the pairof actuators that are activated to open. The actuators can be normallyclosed by a spring (or other means) and only opened when the actuator isenergized. Alternatively they can be normally open.

The product water line 919 connects to a water purification system (linecontinues to a line labeled with the same joining symbol A in FIG. 9).The drain line 920 connects to the water purification system (the linecontinues to a line labeled with the same joining symbol B in FIG. 9. Acontrol line connection (which may be wired or wireless) indicated byconnection symbol C may be provided to connect an internal centralcontroller 959 to the controller 906 to permit commands from thecontroller 906 to be used for controlling the water purification system901. Note that alternatively, instead of a controller 959, a data bus orequivalent communication network such as a wiring harness or wirelesspiconet (not shown) may give direct access to all sensors and finalcontrollers and actuators of the water purification system 901 to thecontroller 906 so that the water purification system is simply acomponent of the peritoneal dialysis system 900. In other embodiments,the water purification system is operable as a stand-alone device andincludes its own user interface and control to supply product water forother functions such as hemodialysis. In embodiments, the functions ofuser interface 906 may be incorporated or included in wireless inputdevices such as a scale 955 or a portable user interface module 956.

A sterile filter 939 is provided to sterile-filter product waterprovided in product water line 919. During, prior to, or afterpreparation of a batch of dialysis solution, the filter may be testedfor leaks by performing a bubble point or pressure decay test. Adelta-pressure transducer (two pressure sensors separated by themembrane) or a single pressure transducer on the air side of a wettedmembrane. In the present embodiment, a transducer at 919 measures thepressure in an air chamber 948 which is in communication with an airside of a wetted membrane of the sterile filter 939. The pressuretransducer 919 is used to detect pressure decay (or in otherembodiments, a transmembrane pressure TMP decay profile) to determine ifthe filter integrity is within expected limits. In the presentembodiment, an air pump 917 draws air through a filter 921 andselectively pumps it through a control valve 923 and a pressure sensor.The pump 917 may run continuously using a pressure regulated valve 918to maintain a desired pressure supply to the valve 923 and the valve 922which may be opened selectively to deliver air into chamber 913B and/or948. The purpose of flowing air into chamber 948 is to perform a bubbleor pressure decay test which is done after making a batch of dialysissolution and to confirm that the filter integrity was maintained duringtransfer of product water. The flowing of air into chamber 948 is donefor the purpose of resetting the volume of the air-side chamber of thepressure pod 951. Air may be selectively leaked from and pumped into thepressure pod to avoid the diaphragm being pinned against one side or theother of its range of travel thereby preventing false readings. So tosummarize, valves 918, 923, and 922 are controlled by controller 907 toregulate pressure (by bypassing flow), and selectively allow air to flowto chambers 913B and/or 945 for the described functions.

Referring now particularly to FIG. 9, the water purification system 901purifies water through a first stage employing a coarse particularand/or sediment trap 994. A second stage employs a carbon filter. Athird stage uses an ultraviolet lamp to decontaminate water. A fourthemploys reverse osmosis. A fifth stage uses a carbon polishing filterwhich is followed by a sixth stage of deionization filtration. A seventhand final stage is a sterilization stage employing a pair ofultrafilters connected in series, which prevents grow-throughcontamination of the final product water, is provided. '901

A permanent filtration subsystem 952 contains a pump, 990 theultraviolet lamp 982, sensor modules 984 and 985, automatic shutoffvalve 988 for the reverse osmosis system, pressure sensors 992, 981,953, 989 and valves 991 and 993.

Drain fluid from drain line 920 passes through a connector 978 and intoa pair of sensor modules 984 and 985 which detect and measureconductivity and temperature, respectively. The sensor modules 984 and985 provide redundancy as a protection against an error in one of themodules. Safety may be ensured, for example, by enforcing a requirementthat the serially interconnected sensor modules 984 and 985 providesignals that are always in agreement and in the event of a disagreement,depending on the operating state, an alarm may be generated or someother action taken. A urea sensor 953 may be used to generate a signalindicating level of urea. The drain line in some modes carries spentdialysate and urea content can be recorded or otherwise used to ensurecorrect treatment of renal dialysis patients according to knownprinciples. The urea level may be displayed on the display 906D orrecorded in a data store of the controller 907 or stored also oralternatively on an Internet server or other external data store (notshown). A check valves 987 at various locations prevent backflow. Onecheck valve 987 in the drain line may be used to prevent backflow intothe peritoneal dialysis system 900. Another check valve 987 preventsdraining fluid backflowing into reverse osmosis filters 975 and anotherprevents prefiltered water flowing from the reverse osmosis filters 975from flowing in reverse. Another check valve 987 prevents primary waterentering the system upstream of the particle filter 994 from flowing inreverse.

In addition to the sensor modules 984 and 985, or alternatively, a fluidquantity measurement module may be provided. Primary water enters thewater purification system 901 through a connector 978 and check valve987 and into a particle filter 994. Filtered water passes through apressure control valve 996, through air vent 999 to a connector 978connecting it to the permanent filtration subsystem 952. A speedregulated pump 990 draws water through a valve 993. Pressures, upstreamand downstream of the pump 990, are measured by sensors 992 and 989respectively. A bypass valve 991 allows water to be recirculated tocontrol pressure. The bypass valve 991 is controlled by the controller955 to regulate pressure exiting the pump 990.

An automatic shutoff valve 988 feeds water to the carbon and ROsubsystem 997 with respective waste water connection, product waterconnection and feed water connections 978. Feed water passes through aconductivity sensor 977, which applies a conductivity signal to thecontroller 955, and then through an activated carbon filter bed.

After passing through RO membranes 975, product water flows throughcheck valve 987 through a line 957 to a pressure sensor 981, through theautomatic shutoff valve 988 to an ultraviolet filter after which productwater leaves the permanent filtration subsystem 952 through a connector978. The connector 978 receiving product water from the permanentfiltration subsystem 952 is a part of a disposable filter module 970containing carbon 963, segregated bed deionization filters 959 (eachwith a cation bed 965 and an anion bed 964) and a mixed bed deionizationfilter 966. The disposable filter module 970 also contains a pair ofseparated ultrafilters 958 with air vents 956. Conductivity sensor 968Adetects early breakthrough of contaminants which may be used by thecontroller 955 to generate an indication that the filter module 970needs to be changed. The indication of expiration of the filter module970 may be output via the user interface panel 906 or an independent one(not shown). The ultrafilters 958 are separated to sterilize and preventgrow-through contamination. A check valve 969 prevents back flow. A fuse960 is blown when the filter module 970 is first connected. Thecontroller 955 prevents the reconnection of filter modules 970 withblown fuses, thereby preventing reuse of previously used filter modules970. A wetness sensor 938 is connected to the controller 955 andgenerates a signal, applied to the controller 955, when a leak wets it.

FIG. 10 shows the peritoneal dialysis system 900 reconfigured as aperitoneal dialysis system that uses prepared dialysate in presterilizedcontainers 1002. Unlike the system 900, the present system does notrequire water purification system 901 in order to work. Fresh dialysissolution bags 1002 are connected to a tubing set 1000 which isconfigured to allow the PD cycler and dialysis solution preparationmodule 949 to be used with prepared bagged dialysate. The PD cycler anddialysis solution preparation module 949 will not be described againexcept to note that the functions of the actuators 929, 930, 928, 931,932, 933, 934, and 935 are in some instances reassigned by the commandsignals of the controller 907.

As may be seen, lines 1010, 1011, 1012, and 1013 connect the dialysissolution bags 1002 to the manifold module 911. At least one of thedialysis solution bags 1002 is attached to a different one of the twovalve headers 941 and 946 to allow transfer of dialysis solution betweenbags, which in turn may allow priming of the tubing set 1000 and otherfunctions. Also note that line 1010 is coupled to the line 945 to allowfluid from either of valve headers 941 and 946 to be pumped into thepatient line 945. The functions enabled by this configuration include,for example, to allow fluid to be conveyed to one of the dialysissolution bags 1002 indicated at 1020 which may be rested on the heater903, from any of the other bags 1002. Then, once bag 1020 is emptied,fluid can be transferred from one of the other bags 1002 to fill it andthe bag 1020 heated prior to infusion. Inspection of the tubing set 1000and valve headers 941 and 946 make it clear that these functions areenabled simply by appropriate sequencing of the 929, 930, 928, 931, 932,933, 934, and 935. Each of the dialysis solution bags 1002 is providedwith a non-reopenable clamp 1005, a needle free port 1007, and matingconnectors 1006 and 1007 on the bag 1002 and tubing set 1000.

FIG. 11 shows an overview of a method for preparing any of the foregoingperitoneal dialysis systems. The left side of the flow chart of FIG. 11shows a method for systems using bagged dialysis fluids and the rightside for ones that prepare dialysis fluids such as system 900. First newbags are hung S10 (in the embodiment 902, one of the bags is placed on aheater). Then a cartridge or tubing set is loaded on the cycler S12. Inbagged fluid systems, the new bags are connected to the tubing set orcartridge S14 and the drain and patient lines connected S16. The bag1020 on the heater is used for the first cycle and may be pre-filled. Inan alternative embodiment the bag on the heater is initially empty andforms a preattached part of the fluid circuit 1000. Later after thefirst cycle, the bag on the heater may be empty and this bag may befilled from one or more of the other bags 1002. Whether filled or not,the bag on the heater 1020 is used for priming S17 by flowing dialysissolution through the fluid circuit and the patient lines S19. Fluid maybe directed through the drain during priming and for testing theconductivity as discussed above.

At S18, a self-testing procedure may be performed, for example, to do apump calibration, check pressure ranges, perform bubble point orpressure decay tests on the sterile filter membrane, etc. The patientaccess is then connected to the patient line and a drain cycle S22followed by a fill cycle S24 performed. The drain and fill cycles may berepeated until a treatment completed check S26 indicates that a completeset of drain and fill cycles has been performed. Remaining fluid in thebags 1002 may be drained S28 and the access, bags, and fluid sets may bedisconnected and disposed of S30 and S32.

Still referring to FIG. 11, a method for the peritoneal system 900 canprepare each batch of dialysate. In the method, the fluid management set900A is loaded on the system including placing the disposable batch,electrolyte, and osmotic agent concentrate containers 908, 910, and 912on the heater and/or scale 902 S40. The remainder of the fluidmanagement set 900A including the manifold module 911 is loaded and thedoor 973 closed to clamp the manifold module 911 against the valveactuators 929, 930, 928, 931, 932, 933, 934, and 935. Alternatively, anyother suitable fluid circuit, such as the examples of FIGS. 8D and 8Eand variants thereof, may be loaded. At S16, the patient and drain linesare connected and at S46, S48, the fluid circuit 900A is primed andflushed if required. The disposable batch, electrolyte, and osmoticagent concentrate containers 908, 910, and 912 connecting lines areprimed S50 and the batch preparation and filter test performed S52. Thepatient lines are primed S19 and the patient access connected S20. Thedrain and fill cycles may be repeated until a treatment completed checkS26 indicates completed set of drain and fill cycles have beenperformed. The disposable batch, electrolyte, and osmotic agentconcentrate containers 908, 910, and 912 are emptied S58 anddisconnected S60 and the drain disconnected at S32.

FIG. 12 shows details of the process within S50 of FIG. 11 in which thedisposable batch, electrolyte, and osmotic agent concentrate containers908, 910, and 912 connecting lines are primed. At S50B, the osmoticagent line 914 is filled and drained through the conductivity cell untilthe conductivity cell shows the presence of fluid at which point S50A,the same is done at S50D for the electrolyte line 913 until electrolyteis detected by the conductivity sensor at S 50C. Recall thatconductivity sensors 984 and 985 may be used for this purpose bydetecting fluid properties in the drain line connected to waterpurification system 901. Next S50F pure product water flushes out anyconcentrate fluid priming the drain line and, primes the product waterline 919 until the lapse of a time interval S50G and the conductivity ofthe product water is confirmed. The batch fill line 919 is then primedand the batch container 908 filled with 200 ml water or more S50G. Wateris drained out of the batch container 908 through the batch containerdraw line 916 until 100 ml has been removed S50J. In an embodiment, avacuum may be applied in the batch container 908 at this point tooptimize repeatability in fluid draw cycles.

FIG. 13 shows details of the process within S52 of FIG. 11 in which abatch of dialysate is prepared by the peritoneal dialysis system 900 orsimilar system. At S52B the batch container 908 is filled with productwater until 1500 ml are displaced, which is detected at S52A. Thequantity is an example only and may vary in different embodiments.Osmotic agent concentrate is then 52D drawn and pumped into the batchcontainer 908 until the total mixed volume of the batch container is1550 ml 52C. The fill state of the batch container may be confirmedvolumetrically or gravimetrically or any other suitable means. Asdiscussed above, in other embodiments, or the present embodiment, theratios of fluids are what is primarily important in terms of forming atarget prescription and the ratiometric proportioning of the presentsystem, as described elsewhere, ensures the electrolyte and osmoticagent ratios and dilution rates are achieved, in addition to, or as analternative to control or confirmation by detection. Next at S52Felectrolyte concentrate is drawn and pumped into the batch container 908until the total mixed volume of the batch container is 1650 ml 52E. Asdescribed above, optionally a mixing step followed by testing of theconductivity may be performed at this point. The batch container 908contents may be mixed by drawing and filling through lines 916 and 917for a period of time S52J or over a predefined number of pump cycles.The mixing may occur multiple times with a rest interval between mixingcycles. This may be followed by additional supplementation ofelectrolyte to achieve the desired prescription. The remaining productwater is pumped into the batch container 908 S52H until at S52G the fillquantity is achieved. At each of S52C, 52E, and 52G the conductivity ofthe contents of the batch container 908 may be checked, for example, byautomatically draining a small sample through the drain of the waterpurification system 901. Then the batch container 908 contents are mixedby drawing and filling through lines 916 and 917 for a period of timeS52J or over a predefined number of pump cycles. The mixing may occurmultiple times with a rest interval between mixing cycles. Conductivityis confirmed and the procedure ends (S52 End) or if the conductivitytest fails (dialysate conductivity not achieved) an alarm is outputS52L. Lastly, the sterile filter integrity is tested with a bubble pointor pressure decay test by pumping air through the membrane S61.

FIG. 14 shows details of the process within S61 of FIG. 11. At S61Bvalve 923 is opened, 918 closed, and air pressure increased asregistered by pressure sensor 919 until, at S61A, pressure reaches apredetermined pressure (e.g. 45 psi) then the air pump is turned off andthe valve 923 closed. At S61D, pressure is monitored (and may beprofiled to generate a decay curve) as indicated by pressure sensor 919for an interval of time, for example 3 minutes S61C. If the pressurefalls below a threshold (e.g. 40 psi) an alarm is output S61F and if not(S61C) the valves 918 and 923 are opened until at S61E the pressure at919 is detected to be below a threshold, for example 10 mm Hg.

FIG. 15 shows the process details of S19 of FIG. 11. FIG. 16 showsdetails of S58 of FIG. 11.

FIGS. 17A through 17T illustrate the method and basic structure of theperitoneal dialysis system according to the foregoing systemembodiments. A batch container 202 has a batch container fill line 222and batch container draw line 224. An osmotic agent concentratecontainer 204 has an osmotic agent concentrate draw line 220. Anelectrolyte concentrate container 206 has an electrolyte concentratedraw line 218. A purified water source 216 such as a water purificationplant has a purified water supply line 223 which feeds water to asterile filter 210 connected by a sterile water supply line 226connecting the sterile filter 210 to a manifold/pumping arrangement 208.A primary drain 228 sends waste and priming fluid to a conductivitysensor 212 and out through a final drain line 230. A patient line 234 isconnected to the manifold/pumping arrangement 208.

The following description applies to a generic PD system and theelements can be configured according to any of a variety of design andtechnology approaches. For example, the manifold/pumping arrangement 208may pump fluid using a diaphragm arrangement or a centrifugal pump andincorporate flow control of any of a variety of sorts includingpermanent valves, flow switches, line clamps etc. The containers batchcontainer 202, osmotic agent concentrate container 204, and electrolyteconcentrate container 206 may be rigid or bag type containers and may bedisposable or permanent with a sterilization plant provided therewith.

FIG. 17A shows the initial priming of the osmotic agent concentrate drawline 220, manifold/pumping arrangement 208 via the primary drain 228 andfinal drain line 230 through the conductivity sensor 212 as describedabove. The manifold/pumping arrangement 208 is configured to provide theflow shown and a controller is provided to change over to the nextconfiguration. In FIG. 17B the manifold/pumping arrangement 208 isconfigured to flow electrolyte concentrate from electrolyte concentratecontainer 206 priming electrolyte concentrate from the draw line 218 viathe primary drain 228 and final drain line 230 through the conductivitysensor 212. In FIG. 17C, water is moved by manifold/pumping arrangement208 from the purified water source 216 through purified water supplyline 223, through sterile filter 210, through 226, and out ofmanifold/pumping arrangement 208 via the primary drain 228 and finaldrain line 230 through the conductivity sensor 212, thereby flushingconcentrate from the manifold/pumping arrangement 208 and the primarydrain 228 and final drain line 230. At each stage, conductivity ismeasured by conductivity sensor 212 and compared to a reference range.If the value is outside the reference range, the production is haltedand an error message is generated.

FIG. 17D shows the initial filling of the batch container 202. Purifiedwater is pumped by manifold/pumping arrangement 208 through purifiedwater supply line 223, sterile filter 210, and sterile water supply line226 into batch container 202 until a predefined small volume istransferred (for example 200 ml). Osmotic agent concentrate draw line220 and electrolyte concentrate draw line 218 remain primed as shown bythe fill pattern. Next, in FIG. 17E, some of the contents (e.g. 100 ml)of the batch container 202 are drained by manifold/pumping arrangement208 out via the primary drain 228 and final drain line 230 through theconductivity sensor 212 and the conductivity determined and subsequentcontrol processing continues (halts and alarms) depending on the result.In FIG. 17E, the manifold/pumping arrangement 208 is configured topartly fill the manifold/pumping arrangement 208 by drawing water fromthe purified water source 216 through sterile filter 210 and sterilewater supply line 226 and finally into the batch container 202 via batchcontainer fill line 222. The batch container draw line 224, osmoticagent concentrate draw line 220, and electrolyte concentrate draw line218 remain primed as do the primary drain 228 and final drain line 230.

In FIG. 17G, a sample from the batch container 202 is drawn bymanifold/pumping arrangement 208 and drained via the primary drain 228and final drain line 230 through the conductivity sensor 212. Again, thefluid properties are verified by the conductivity sensor 212 and passedor alarmed. In FIG. 17H, osmotic agent is drawn from osmotic agentconcentrate container 204 via an osmotic agent concentrate draw line 220by manifold/pumping arrangement 208 and pumped into batch container 202through batch container fill line 222. In FIG. 17J, a sample from thebatch container 202 is drawn by manifold/pumping arrangement 208 anddrained via the primary drain 228 and final drain line 230 through theconductivity sensor 212. Again the fluid properties are verified by theconductivity sensor 212 and passed or alarmed.

In FIG. 17K, electrolyte is drawn from electrolyte concentrate container206 via electrolyte concentrate draw line 218 by manifold/pumpingarrangement 208 and transferred to batch container 202 via batchcontainer fill line 222. In FIG. 17L, a sample from the batch container202 is drawn by manifold/pumping arrangement 208 and drained via theprimary drain 228 and final drain line 230 through the conductivitysensor 212. Again the fluid properties are verified by the conductivitysensor 212 and passed or alarmed. In FIG. 17M, purified water is drawnby manifold/pumping arrangement 208 through purified water supply line223, sterile filter 210, and 226 and transferred to batch container 202via batch container fill line 222. In FIG. 17N, a sample from the batchcontainer 202 is drawn by manifold/pumping arrangement 208 and drainedvia the primary drain 228 and final drain line 230 through theconductivity sensor 212. Again the fluid properties are verified by theconductivity sensor 212 and passed or alarmed.

FIG. 17P shows a fluid mixing configuration in which themanifold/pumping arrangement 208 is configured to circulate fluidthrough batch container 202 via the batch container fill line 222 andbatch container draw line 224. This is done for a predefined period oftime, predicted number of fluid cycles or number of pump cycles. In FIG.17Q, a sample of the final dialysate product from the batch container202 is drawn by manifold/pumping arrangement 208 and drained via theprimary drain 228 and final drain line 230 through the conductivitysensor 212. Again, the fluid properties are verified by the conductivitysensor 212 and passed or alarmed. If the fluid formulation needs to beadjusted, a small amount of osmotic agent concentrate or electrolyteconcentrate or diluting water can be added and the test repeated untilthe desired formulation is reached.

FIG. 17R shows fluid drawn by manifold/pumping arrangement 208 throughbatch container draw line 224 and out the patient line 234 to prime thelatter. In FIG. 17S the access for the patient 214 has been connected tothe patient line 234 and a drain operation is performed in which spentdialysate is drawn from the patient 214 through the patient line 234 bythe manifold/pumping arrangement 208 and passed out through via theprimary drain 228 and final drain line 230 through the conductivitysensor 212. Detected conductivity and pressure change can be used todiagnose problems such as the permeability of the peritoneal membrane,infection, etc. as discussed above. FIG. 17T shows a patient fill cyclewhere fluid is drawn from the batch container 202 by themanifold/pumping arrangement 208 and pumped into the patient line 234and into the patient 214.

In the embodiments of FIGS. 17A through 17T, the manifold/pumpingarrangement 208 may include a controller, user interface, valves, one ormore pumps, sensors, flowrate sensors, volumetric displacement sensors,and/or other components to achieve the stated functions.

In any of the foregoing embodiments, the osmotic agent concentrate mayinclude a predefined portion of electrolyte concentrate permitting thequantity or concentration of osmotic agent to be determined by measuringthe electrolyte concentration using a conductivity cell. The finalelectrolyte concentration is achieved by proportioning the electrolyteconcentrate based on the known amount delivered with the osmotic agentconcentrate.

FIG. 18 illustrates a control system according to embodiments of thedisclosed subject matter. A controller 830 may receive sensor signalsfrom any points in a PD system 838 including conductivity, temperature,and flow rate. The controller may apply actuator control signals toregulate the speed of pump or an equivalent flow rate regulator such asa fixed rate pump with a variable recirculation bypass line or variableinline resistance such as a flow regulator valve. Fluid provided fromthe PD system 838 is transferred at a regulated rate to a peritonealline 842, which may include a single line used for outgoing and returnfluids or a pair of lines, each used respectively for outgoing andreturn fluids. A pressure sensor 834 generates signals indicating thepressure at a distal point in an outgoing peritoneal line or aperitoneal line that transfers fluids in both directions. An additionalpressure sensor may be used for outgoing and return lines, respectively.A data store 836 may store one or more treatment profiles specific to adisposable unit that includes a fluid circuit (which may vary accordingto characteristics of the fluid circuit), specific to a particularpatient or class of patients, or other requirement.

Pressure profile data stored on data store 836 may be obtained from adata store 841 attached to the disposable unit or may be downloaded froma server based on identifying information on such a data store 841.Alternatively pressure profile data may be stored on the 836periodically and specific data to be used for a treatment selected froma user interface of the controller during treatment, for example datafor a particular patient identified through the user interface and whoseprofile data is obtained from a repository of patient-specific treatmentdata. The pressure profile data may include a single pressure valuerepresenting a maximum pressure at the point of the pressure sensor 834indicating a maximum pressure and serving as a limit on the pumping rateby pump 840 as controlled by the controller 830 as described accordingto any of the foregoing embodiments. The pressure profile data mayinclude multiple pressure values representing respective phases of aperitoneal dialysis fill cycle. For example, the pressure values maycorrelate volume and pressure or number of pump rotations and pressurethus defining a profile. In example, the rate may be rampedprogressively up toward a maximum and then slowed gradually to balancethe desires of speedy throughput and patient comfort.

FIG. 19 shows a fluid path and actuator layout according to embodimentsof the disclosed subject matter. The present embodiment shows variationson the embodiments described above. For example, separate fill 861 anddrain 862 lines are connected to the patient (a single lumen or duallumen peritoneal catheter). A sterile filter 860 is provided in the fillline. One or more flow sensors may be provided, for example as shown at854 and/or 855, which may be used for error condition detection or forimplementing a calibration procedure to derive the conversion of pumpcycles to net displaced mass or volume respective of each flow path, asdescribed above. Respective valves G1, P1, P1, P2, S1, S1, W1, and E1control the flow of fluids in the circuit. A pump 858 moves fluid in thecircuit. The following table shown an embodiment of an operationalprocedure for the embodiments covered by FIG. 19. Any of these featuresmay be combined in any of the foregoing embodiments to form additionalembodiments. For example, the one or more flow sensors may be providedin the embodiments of FIGS. 6A to 6K or 7A to 10, or 17A to 17T. Themethod embodiments may be modified to add the calibration procedureoutlined above as well.

Valve State Mode Description Pump Operation G1 E1 W1 S1 S2 P1 P2 D1 1.Prime Osmotic Do until A pump O X X X X X X O agent cycles 2. Prime Dountil A pump X O X X X X X O Electrolyte cycles 3. Prime Water to Dountil B pump X X O X X X X O Drain (flush cycles concentrate) 4. PrimeWater to Do until C pump X X O O X X X X SAK cycles 5. Prime Mixing Dountil D pump X X X O O X X X Circuit cycles 6. Prime SAK to Do until Epump X X X X O X X O Drain (measure cycles flow rate) 7. Prime PatientDo until F pump X X X X O X O X Line (V1) cycles 8. Prime Patient Dountil G pump X X X X X O X O Line (V2) cycles 9. Add Osmotic Do until H(calc) O X X O X X X X agent to SAK pump cycles 10. Add Do until I(calc) X O X O X X X X Electrolyte to pump cycles SAK 11. Add Water toDo until J (calc) X X O O X X X X SAK pump cycles 12. Mix Do until K(calc) X X X O O X X X pump cycles 13. Test Sample Do until L pump X X XX O X X O (Temp/Condo/ cycles Flow) 14. Rinse Fluid Do until O pump X XX X O X X O Path w/Dialysate cycles 15. Drain Patient Do until N (calc)X X X X X O X O pump cycles OR PRES > Fill_Pres_Limit 16. Fill PatientDo until M (calc) X X X X O X O X pump cycles OR PRES > Drain_Pres_Limit17. Patient Dwell Do until TIME — — — — — X X — COUNT 18. Empty batch Dountil P (calc) X X X X O X X O container pump cycles

In the second column, Pump Operation, the letters A, B, C, etc. refer topredefined values. For example, a peristaltic pump may rotate once forevery 2 ml. pumped so the values may correspond to an amount of fluidpumped. The columns labeled Valve State refer to the status of the valveas labeled in FIG. 19, with X referring to a closed condition and Oreferring to an open condition. The term (calc) in the Pump operationcolumn indicates that the number of pump cycles is adjusted according toa parameter obtained from calibration as discussed above.

In any of the disclosed and/or claimed method, control, or systemembodiments, in which the batch container is emptied, a negative pumpingpressure may be applied to the container for a period of time to ensurecomplete emptying. Also, in any of the disclosed and/or claimedembodiments, the batch container may be positioned on an angled basewith its drain opening at a lowest point, also to help in fully emptyingthe batch container. Other embodiments may be formed by providing amechanism for jostling or vibrating the batch container and/or the otherfluid containers to help ensure fluid is not trapped.

In any of the foregoing manifold embodiments, the drain line can besplit to valves on both sides of the pump tube, as in the embodiments ofFIGS. 7A, 7B, and 8A or the patient line can be split to valves on bothsides of the pump tube as in FIGS. 10 and 19. When the drain line issplit, the pump may need to be reversed in order to fill and drain thepatient's peritoneum. By splitting the patient line, the manifold andpump can be constructed and operated so that the pump only needs to runin a single direction in order to provide all of the required functionsaccording to embodiments in which: (1) the water, treatment fluidcomponents, and one batch container outlet are all connected throughrespective control valves to the pump inlet and the batch inlet anddrain are connected through respective control valves to the pump outletand (2) the patient line is connected to both the pump inlet and outletthrough respective control valves. By running the pump in a singledirection, the repeatability of the conversion from pump cycles tofluids transferred can be better maintained. In an alternativeembodiment, fluid is drained from the patient by a separate pump line.This may be done by a dual lumen peritoneal line or by a single lumenline.

In any of the foregoing embodiments, separate fill and drain lines canbe used instead of a single fill/drain line. In embodiments withseparate fill and drain lines, a pressure pod may be carried on the fillline alone, the drain line alone, or pressure pods may be provided onboth the fill and the drain line. The same is true for other pressuremeasurement embodiments of peritoneal treatment lines. As will beevident, the pressure measurement capabilities may be used for thedetection of spent dialysis fluid properties and for the regulation offilling flow rate and other purposes described herein.

In the present and any of the other embodiments, a sufficient amount offluid may be drained in order to contact the conductivity sensor to forma reliable reading. For example, an amount in the range of 25 to 100 mlor preferably an amount in the range of 50-70 ml. may be used.

In any of the described embodiments, the osmotic agent may be, orinclude, glucose, L-carnitine, glycerol, icodextrin, or any othersuitable agents. Further, the components combined to make a peritonealdialysis solution may vary in number and any of the embodimentsdescribed could be made from single concentrate components or any othernumber of concentrate components by straightforward modifications of theembodiments. For example, a buffer (e.g., acetate, bicarb, lactate) maybe separate from an electrolyte which may be separate from an osmoticagent.

In any of the disclosed embodiments that employ direct attachment ofdiluted fluids, for example, the embodiment of FIG. 10, sterile filtersmay be preinstalled on fluid lines, (e.g., lines 1010, 1011, and 1012)to prevent touch contamination from causing contamination of the fluidthat flows to the patient.

In any of the disclosed embodiments, pressure signals that proximal anddistal ends of the peritoneal line may be generated while a no-flow, orlow-flow, condition exists. This may be controlled to occur at a certainpoint in preparation for, or during treatment, to generate indicationsof static hydraulic head in the line. For example, if a patient fallsout of bed, and a sudden height difference between the proximal anddistal ends arises, a pressure difference may be detected. The detectionmay trigger an alarm or other output and may instantiate a change inmachine status for example a shutdown. Another inference from an out ofbounds pressure difference during low or no flow is abnormal set up thesystem. In embodiments, the conversion of pump cycles to totaltransferred flow may be governed by assumed system configuration whichmay include a certain range of height differences between the proximaland distal ends of the peritoneal line. The following table shows somepossible behaviors.

Machine status Detected conditions Response Low or no flow DP outsiderange A Generate alarm indicating (e.g., dwell) misconfiguration. FillDP outside range B Generate alarm indicating misconfiguration Fill DPoutside range C Adjust flow rate and/or shut down flow. Drain DP outsiderange D Generate alert message indicating possible infection. Drain DPoutside range E Generate alarm indicating misconfiguration Drain DPoutside range F Adjust flow rate and/or shut down flow. Any time theline Pulse or respiration Indicate status of connection is filled withfluid detected, or stronger is ok. than threshold G, at Proximal sensorAny time the line Pulse or respiration not Indicate connection is isfilled with fluid detected or weaker than misconfigured or possiblythreshold G at Proximal misconfigured. sensor and is detected at distalsensor Dwell Pulse or respiration Indicate status of connectiondetected, or stronger is ok. than threshold H, at Proximal sensor DwellPulse or respiration Indicate connection is detected, or weaker thanmisconfigured or possibly threshold H, at distal misconfigured. sensorAny time line is Pulse or respiration Indicate line is filled with fluiddetected at distal sensor misconfigured or and not at proximal possiblymisconfigured. sensor Fill Proximal P high, distal Indicate obstructionP low between

In the table above, ranges identified by letter may represent pressureprofiles, that is pressure values (upper and lower limits or just upperor just lower limits) that change during a progressive process. Forexample, pressure range C may ramp up with the number of pump cycles.The range data may be stored in a memory of the controller and/or may bestored on a memory device of the replaceable tubing set and/or may beread from a remote server or derived by any other suitable system. Thepressure range data may be respective to a particular tubing set model,treatment type, and/or patient and selection may be automated or mademanually through a user interface. The term misconfiguration can referto kinks, obstructions, leaks, disconnections, or other types of lineproblems. In the table, anywhere alarm or other output is indicated asan action, this may include, or be in the alternative, instructing theuser to take some action to verify the problem or a detailed explanationof what the action might be. For example, if a misconfiguration of theconnection is indicated, the

In any of the disclosed embodiments, the distal pressure sensor may belocated within a peritoneal cycler machine or on the tubing set leadingto the patient and close to the machine. The distal pressure sensor maybe located near the patient and on the tubing set or within a peritonealcatheter. It may also be separated from the tubing set and positionedwithin the peritoneum. In such an embodiment, the pressure sensor linesmay be attached to the tubing set. For example, metallized surface ofthe tubing or a co-extrusion (wire insulation and tubing beingcoextruded) or simply attached to the tube at points therealong.

In any of the disclosed embodiments, an osmotic agent, concentrated ordilute, or a peritoneal dialysis solution or concentrate thereofcontaining glucose or any other precursor of a dialysis solution maycontain glucose that has not been treated with heat. In any of theseembodiments, the glucose concentrate or solution or dialysis solution orprecursor containing glucose may be sterile filtered as it is stored ina sterile container without using heat sterilization at all. This avoidsheat sterilization byproducts of glucose that are toxic. In a methodembodiment, the a sterile package including a bag has an inlinesterilizing filter (e.g., 0.1 micron porosity sterilizing filter) at afilling port thereof. The port may be elongate and have a nonreopenableclosure on the filling port. Another port, sealed at the time offilling, may be used to access the contents. Before filling, the sealedcontainer is sterilized by gamma sterilization or heat sterilization.Then the glucose solution is pumped into the container through theinline sterile filter and the nonreopenable closure feature is closed.The nonreopenable feature can be just a weldable tube neck which issealed by thermoplastic welding. Other sealing devices may be used.

According to embodiments, the disclosed subject matter includes a methodof performing a dialysis treatment. The method uses a dialysate supplyline that has proximal end into which peritoneal dialysis fluid issupplied and from which spent dialysate is withdrawn and a distal endwhich is connected to a patient's peritoneal access. The method includesgenerating proximal and distal pressure signals using pressure detectorslocated at both the proximal and distal ends, respectively, of thesupply line. The method further includes supplying peritoneal dialysisfluid at a rate that is responsive to the distal and pressure signals.For example, the peritoneal dialysis fluid may be supplied at a variablerate which is adjusted by a controller responsively to both (i.e., acombination of) the distal and proximal pressure signals. For example,the pressure drop may be calculated by the controller and that pressuredrop used to regulate flow. For example, the pressure drop may representa viscosity characteristic or a kink in the fluid lines. The viscositycharacteristic could be viscosity which might indicate a disease such asperitonitis. Another example is that a pressure difference may arise asa result of the patient being at a very high or low position relative tothe peritoneal dialysis cycler unit. In the latter case, the fall of apatient off his bed may be indicated and this indication used togenerate an alarm. So the controller may have predefined operatinglimits of pressure difference, each limit may be tied to a particularflow range or flow rate or status of the machine and used to infer somestatus that is either normal or erroneous. Thus, the methods disclosedinclude ones in which the aforementioned supplying operation includescalculating a characteristic of the dialysate supply line and supplyingperitoneal dialysis fluid at a rate that is responsive to thecharacteristic. The methods disclosed also include ones in which theaforementioned supplying operation includes calculating a characteristicof the dialysate supply line and generating an output that is responsiveto the characteristic. The outputs may be a text or audible output usinga user interface of the cycler and connected to a controller. Outputscan also be sent to remote locations such as a clinic that monitors hometreatment or an automated cellular phone message or call. The disclosedmethods may thus also include those where the supplying includescalculating a height of a fluid column responsively to the difference inthe proximal and distal pressures and supplying peritoneal dialysisfluid at a rate that is responsive to the height. The supplying mayinclude varying a rate of pumping of dialysate responsively to adifference between the proximal and distal pressure signals such that aninput pressure of fluid at a point of entry into the peritoneum ismaintained, the input pressure corresponding to a predefined pressurestored in a controller that controls a rate of the supplying. Thesupplying may be effective to limit a pressure difference determined bya controller between the proximal and distal pressure signals. Thesupplying may be effective to limit a pressure indicated by the distalpressure signal received by a controller that controls a rate ofpumping.

According to embodiments, the disclosed subject matter includes a methodof performing a dialysis treatment in which a pump and a dialysatesupply line are used. The supply line has a proximal end into whichperitoneal dialysis fluid is supplied and from which spent dialysatewithdrawn. Note that the method may be used with a dual lumen line. Thedistal is connected to a patient's peritoneal access. The methodincludes supplying peritoneal dialysis fluid to the peritoneum of a livepatient while generating proximal and distal pressure signals, thegenerating including using pressure detectors positioned at both theproximal and distal ends. The method includes reducing the flow rate ofdialysis fluid or halting the flow of dialysis fluid when the differencebetween the proximal and distal pressure signals rises above a thresholdvalue. The reducing may include using a controller to calculate, fromthe proximal and distal pressure signals, a characteristic associatedwith a difference in the proximal and distal pressure signals andreducing the flow rate responsively to the characteristic or generatingan alarm indication indicating a problem with the supply lineresponsively to the proximal and distal pressure signals when thedifference between the proximal and distal pressure signals rises abovethe threshold value. Alternatively it may include reducing the flow rateof the supplying responsively to the proximal and distal pressuresignals when the difference between the proximal and distal pressuresignals rises above the threshold value; halting the flow rate of thesupplying responsively to the proximal and distal pressure signals whenthe difference between the proximal and distal pressure signals risesabove the threshold value; and/or recording a digital record of an errorevent in a non-volatile data store responsively to the proximal anddistal pressure signals.

According to embodiments, the disclosed subject matter includes a methodof performing a dialysis treatment using a pump and a dialysate supplyline to transport peritoneal dialysis fluid. The supply line has aproximal end into which peritoneal dialysis fluid is supplied and fromwhich spend dialysate is withdrawn (or a combination line with twolumens, one for filling and one for draining), and a distal end which isconnected to a patient's peritoneal access. The method includesgenerating proximal and distal pressure signals using pressure detectorslocated at both the proximal and distal ends, respectively, of thesupply line. The method may include, during a drain cycle in which spentdialysate is pumped from the patient, responsively to the proximal anddistal pressure signals, detecting a characteristic of a pressuredifference between the distal and proximal ends whose magnitude isdetermined by a predicted change in dialysate properties, andresponsively to the characteristic, generating a signal indicating thechange in dialysate properties.

The change in dialysate properties may include an increase in viscositythat causes an increase in pressure drop and the method may includegenerating a display indicating a change in viscosity, the indication ofa possible disease condition or other kind of message or alarm. Themethod may include recording in a non-volatile data store, an indicatorof a pathology event including an identifier of the dialysate propertiesand an identifier of a patient or transmitting a message to a careprovider service, the message indicating the pathology event.

According to embodiments, the disclosed subject matter includes amedical treatment device employing a treatment machine configured topump a medicament to a patient. The treatment machine has a flow linehaving a proximal end located at the treatment machine and a distal endattachable to a patient access. A proximal pressure sensor is positionedto detect a pressure in the flow line proximal end. A distal pressuresensor is positioned to detect pressure in the flow line at the distalend. The distal pressure sensor includes an in-line pressure pod at thedistal end with an air line running parallel to, and attached atmultiple points along, the flow line. The air line is connected at oneend to the pressure pod and at the other end to a pressure sensingassembly located at the treatment machine. The air line may be tubingline filled with air. Alternatively, the pressure pod and air line mayemploy a different working fluid from air, for example, a gas or liquid.The treatment machine may be a peritoneal cycler configured to provideautomated peritoneal dialysis. The treatment machine may include acontroller configured to implement any of the described methods.

According to embodiments, the disclosed subject matter includes amedical treatment device the includes a treatment machine configured topump a medicament to a patient. A flow line with a proximal end locatedat the treatment machine and a distal end attachable to a patient accesshas a proximal pressure sensor positioned to detect a pressure in theflow line proximal end. A distal pressure sensor is positioned to detectpressure in the flow line at the distal end. The distal pressure sensorincludes a distal pressure transducer at the distal end. The distalpressure transducer includes a semiconductor that is subjected topressure from fluid in the fluid line on at least one side thereof andthereby arranged to detect a pressure at the distal end of the fluidline. The pressure transducer may be arranged to be fully immersed influid when the fluid line is conveying fluid. The treatment machine maybe a peritoneal cycler. The treatment machine may include a controllerconfigured to implement any of the disclosed methods.

According to embodiments, the disclosed subject matter includes a methodof performing a dialysis treatment using a pump and a dialysate supplyline, where the supply line has a proximal end into which peritonealdialysis fluid is supplied and from which spent dialysate is withdrawn,and a distal end connected to a patient's peritoneal access. The methodincludes supplying peritoneal dialysate to the peritoneum of a livepatient to generate a pressure signal, using a pressure detectorconnected to the supply line. The method further includes generating anindicator signal indicating a presence of the respiratory or heart rateor indicating a magnitude of the respiratory or heart rate and/or analarm condition responsively to the pressure signal. The generating mayinclude applying a characteristic of the pressure signal to a classifierand using the classifier, comparing the characteristic signal to atleast one predefined parameter; and generating the indicator signalresponsively to a result of the comparing.

According to embodiments, the disclosed subject matter includes a methodof performing a dialysis treatment using a pump and a dialysate supplyline, the supply line having a proximal end into which peritonealdialysis fluid is supplied and from which spent dialysate is withdrawn,and a distal end connected to a patient's peritoneal access. The methodincludes filling the supply line with peritoneal dialysis solution anddetecting a patient's respiratory or heart rate from the distal pressuresignal using a pressure detector located at the distal end of the supplyline and outputting a signal responsive thereto. The filling may includeflowing peritoneal dialysis fluid through the supply line. The methodmay include applying the status signal to a controller and using thecontroller, altering a rate of the flowing responsively to the signal.

According to embodiments, the disclosed subject matter includes a methodof performing a dialysis treatment using a pump, filling a supply linewith peritoneal dialysis solution, the supply line having a proximal endinto which dialysis fluid is supplied and from which spent dialysate iswithdrawn, and a distal end which is connected to a patient'speritoneum. The method includes generating proximal and distal pressuresignals using pressure detectors located at both the proximal and distalends, respectively, of the supply line. The method further includesresponsively to the proximal and distal pressure signals, detecting apatient's breathing or blood pulse to generate respective proximal anddistal respiration signals. The method further includes recording dataresponsive to at least one of the proximal and distal respirationsignals on a non-volatile data store. The supply line may include aperitoneal catheter and the distal end coincides with the peritonealcatheter. The generating the distal pressure signal may include using apressure detector located on a peritoneal catheter.

According to embodiments, the disclosed subject matter includes a methodof performing a dialysis treatment using a pump and a dialysate supplyline, the supply line having a proximal end into which peritonealdialysis fluid is supplied and from which spent dialysate is withdrawn,and a distal end which is connected to a patient's peritoneal access.The method includes generating proximal and distal pressure signalsusing pressure detectors located at both the proximal and distal ends,respectively, of the supply line. The method further includes,responsively to the proximal and distal pressure signal, detecting apatient's breathing or blood pulse to generate respective proximal anddistal respiration signals, and generating an alarm signal responsive toa combination of the proximal and distal respiration signals. Thecombination may be a difference between levels of the proximal anddistal respiration signals and the alarm signal indicates a loss ofpatency in the supply line. The recording may include recording areliability metric corresponding to the data, the reliability beingresponsive to a level of the corresponding respiration signal.

According to embodiments, the disclosed subject matter includes amedical treatment device that includes a treatment machine configured topump a medicament to a patient and a flow line having a proximal endlocated at the treatment machine and a distal end attachable to apatient access. A proximal pressure sensor is positioned to detect apressure in the flow line proximal end. A distal pressure sensor ispositioned to detect pressure in the flow line at the distal end. Thedistal pressure sensor includes a distal pressure transducer at thedistal end, the distal pressure transducer including a semiconductorthat is subjected to pressure from fluid in the fluid line on at leastone side thereof and thereby arranged to detect a pressure at the distalend of the fluid line.

According to embodiments, the disclosed subject matter includes a methodof performing a peritoneal dialysis treatment that begins withconnecting a disposable unit to a source of water where the disposableunit includes at least a first container holding a sterile concentratecontaining an osmotic agent, a second container holding a sterileconcentrate containing electrolytes, an empty sterile mixing container,and a tubing set with a pre-attached peritoneal fill/drain line. Themethod includes receiving a prescription command by a controller,indicating at least the fill volume and desired final concentration ofthe osmotic agent to be used for a current fill cycle under thetreatment. The method further includes using the controller, pumping aquantity of the concentrated osmotic agent that is at least sufficientto achieve the desired final concentration into the mixing container,mixing the contents of the mixing container, and further diluting orfurther adding concentrated osmotic agent to the mixing container. Themethod also includes flowing fluid from the mixing container to apatient. Prior to the pumping a quantity of the concentrated osmoticagent and responsively to the prescription command, the controller maybe used to pump a volume of water from the source of water into themixing container. After the mixing, the concentration of osmotic agentin the mixing container may be detected. The first container may hold asterile concentrate containing both an osmotic agent and a predefinedmixture containing electrolytes, the mixture serving as a marker for thepurpose of establishing a conductivity versus concentrationcharacteristic that is monotonic within a range suitable for closed-loopcontrol. The method may include pumping into the mixing container aquantity of the concentrated electrolytes from the second containerthat, in combination with the selected quantity of concentrate pumpedfrom the first container, will result, upon further dilution, in thedesired final dialysis fluid formulation.

The method may further include mixing the contents of the mixingcontainer, detecting the total concentration of electrolytes in themixing container, further diluting or further adding concentratedelectrolytes to the mixing container, and flowing fluid from the mixingcontainer to a patient. The electrolyte marker may be the same speciesas the electrolyte concentrate held in the second container. Thedetecting the concentration of osmotic agent may include detecting theconcentration of the electrolyte marker using a conductivity sensor,whereby the concentration of the osmotic agent is inferred from anattending concentration of electrolyte. The electrolyte marker andosmotic agent may have been proportioned such that only concentrate fromthe first container is needed when the prescription command calls forthe maximum desired concentration (typically 4.25% for osmotic agent).The disposable unit may also include a third container holding a buffer.The pH of the concentrated osmotic agent held in the first container maybe less than 4.0 and the pH of the concentrates held in the secondand/or third containers is such that the pH of the final formulationwill be in the range of 6.0 to 8.0. The osmotic agent may includeglucose. The disposable unit may include a sterilizing-grade filter. Themethod may include passing water from the source through thesterilizing-grade filter prior to flowing into the mixing container andconfirming the integrity of the filter prior to supplying fluid to apatient. The method may further include passing the contents of thefirst and second containers, through the sterilizing-grade filter priorto flowing into the mixing container, and confirming the integrity ofthe filter prior to supplying fluid to a patient. The volume of watermay be initially less than 110%, and preferably less than 100%, of theprescribed fill volume. The dialysis treatment may include multiple fillcycles, and the fill volumes and desired final concentrations of theosmotic agent may vary from cycle to cycle.

According to embodiments, the disclosed subject matter includes anothermethod of creating a batch of peritoneal dialysate. The method includesproviding a container pre-filled with a first concentrate containing anosmotic agent combined with electrolytes in a predefined ratio andtransferring a quantity of the first concentrate from the container to abatch mixing container. The method further includes measuring theconcentration of electrolyte in the batch mixing container andcorrecting it by diluting or adding further amounts of the firstconcentrate to the batch container. The correcting may include dilutingthe mixture in the batch container. The method may further includereceiving a prescription command indicating an amount of osmotic agentto be used for a treatment. The correcting may be responsive to theprescription command. The receiving a prescription command may includedetecting and storing parameters of spent dialysate from a priortreatment of a current patient to be treated, reading the storedparameters, and generating the prescription command responsively to thestored parameters.

According to embodiments, the disclosed subject matter includes aperitoneal dialysis disposable unit. The unit has a manifold unitcontaining a mechanism for selectively interconnecting a first array offluid paths, respectively, with a second array of fluid paths, theinterconnecting being completed through a pumping portion and a primaryinlet fluid path of the first array of the manifold unit being connectedto a source of purified water. The unit further includes respectivefluid paths of the second array of the manifold unit being connected toa first container holding a sterile, concentrated osmotic agent and anempty sterile mixing container and a fluid path of the first array ofthe manifold unit being connected to a tubing set that includes apre-attached peritoneal fill/drain line. The first container may containa mixture of a sterile osmotic agent and electrolytes in a predefinedconcentration ratio effective to permit a concentration of theelectrolytes to be detected and thereby function as a marker toestablish a conductivity versus concentration characteristic that ismonotonic within a range of concentrations suitable for peritonealdialysis. The fluid path that connects to a source of purified water mayinclude an inline sterilizing filter. The fluid paths may define aclosed, sterile system, which is accessible to the outside environmentonly through the primary inlet fluid path and the tubing set, both ofwhich are sealed by a removable seal. In the foregoing system, an airline may connect a pressure pod on the peritoneal fill/drain line with apressure transducer. The pumping portion may include a pumping tubesegment. The pumping portion may include only one pumping tube segment.

According to embodiments, the disclosed subject matter includes aperitoneal dialysis disposable unit that has a manifold portioncontaining selectably closable portions. A source connector isconfigured to connect the manifold to a source of purified water. Theunit includes an osmotic agent container filled with osmotic agent, anelectrolyte container filled with sterile electrolyte, and an emptysterile mixing container and a tubing set with a pre-attached peritonealfill/drain line. The osmotic agent container, the electrolyte container,and the empty sterile container are connectable to the source throughthe manifold. The manifold portion is configured to permit the flowingof fluid between the osmotic agent container, the electrolyte container,and the source connector to the mixing container through the samepumping tube portion, without unsealing making or breaking connectionsof the disposable unit.

A controller may be configured to control an actuator adapted to flowfluid through the disposable units of any of the foregoing units. Thecontroller may be programmed to calculate respective flowcharacteristics of respective flow paths connecting the mixing containerto the source connector, the osmotic agent container, and theelectrolyte container at a first time and later use the calculated flowcharacteristics to control quantities of fluid from flowed from sourceconnector, the osmotic agent container, and the electrolyte container tothe mixing container. The controller may be programmed to calculate therespective flow characteristics of respective flow paths by commandingan actuator mechanism to flow fluid through the disposable unit andrecording sensor signals indicating flow rates of the fluid. Thecontroller may be further programmed to detect the connection of thedisposable unit and to calculate the respective flow characteristicresponsively to a detection of a connection of the disposable unit. Thecontroller may be programmed to calculate the respective flowcharacteristics by pumping fluid while simultaneously measuring flowrate using a flow sensor connected to a pump outlet.

According to embodiments, the disclosed subject matter includes aperitoneal dialysis device with a disposable tubing set including a fillline with a patient access connector at one end and a dialysis fluidreceiving end opposite the patient access connector end. A fill-sidepressure measuring sensor is attached at the fill end and forming adisposable component of the tubing set. A patient-side pressuremeasuring sensor is located at the fluid receiving end. The patient-sideand fill-side pressure measuring sensors are adapted for measuringpressure in the fill line at the respective ends thereof. A controlleris configured to regulate a rate of flow in the fill line responsivelyto a signal from the at least the patient-side pressure measuringsensor. The controller may be configured to regulate flow in the fillline responsively to signals from at least the fill-side andpatient-side pressure sensing devices.

According to embodiments, the disclosed subject matter includes aperitoneal dialysis device with a disposable tubing set including a fillline with a patient access connector at one end and a dialysis fluidreceiving end opposite the patient access connector end. A patient-sidepressure measuring sensor is located at the fluid receiving end. Thepatient-side pressure sensing device is adapted for measuring pressurein the fill line at the patient end of the fill line. The deviceincludes a peritoneal dialysis cycler with a controller configured toregulate a rate of flow in the fill line responsively to a signal fromat least the patient-side pressure sensing device. The patient-sidepressure sensing device may be positioned at a distance no greater than20 cm from the access connector. The patient-side pressure sensingdevice may include a pressure pod type device having an air side and afluid side, the air side being in fluid communication with a signal linerunning along the length of the fill line to connect to a pressuretransducer at the cycler location. The patient-side pressure sensingdevice may include a pressure transducer in signal communication withthe controller.

According to embodiments, the disclosed subject matter includes a methodof performing peritoneal dialysis treatment, including conveyingdialysis fluid to a peritoneal cavity through a catheter during apatient fill phase and allowing the dialysis fluid to dwell within theperitoneal cavity during a patient dwell phase. The method furtherincludes conveying dialysis fluid away from the peritoneal cavitythrough the catheter during a patient drain phase and sensing anintraperitoneal pressure through the catheter via a pressure detectingdevice located at an end of a fill line and adjacent to the catheter toregulate the amount of fluid conveyed during the patient fill phase, sothat the peritoneal cavity is not overpressurized during the treatment.The method may further including repeating the conveying, dwelling, andsensing at least once. At least one of the conveying dialysis fluid tothe peritoneal cavity and conveying dialysis fluid away from theperitoneal cavity further may include pumping the dialysis fluid. Thesensing may be performed during the fill phase.

According to embodiments, the disclosed subject matter includes a methodof performing a dialysis treatment including storing a therapeuticprogram in a memory of a controller, the program including pressure datacharacteristic of a target pressure profile having at least two pressuremagnitudes, each corresponding to a respective total quantity ofdialysis fluid transferred during a peritoneal fill cycle. The methodincludes using a pump and a dialysis fluid supply line that has aproximal end into which peritoneal dialysis fluid is supplied and fromwhich spent dialysis fluid is withdrawn, and a distal end which isconnected to a patient's peritoneal access to retrieve the pressure dataand supplying peritoneal dialysis fluid to the peritoneum of a livepatient while applying to the controller pressure signals representingpressure of dialysis fluid at the distal end using a pressure detectorlocated at the distal end. A rate of the supplying is responsive to thepressure signals and the pressure data. The rate of the supplying may beresponsive to a cumulative quantity of dialysis fluid transferred thatis calculated by the controller. The pressure target pressure profilemay include data representing a series of pressures that are initiallyhigh and fall to a lower rate at higher levels of total dialysis fluidtransferred. The supplying may include varying a rate of pumping ofdialysate responsively to a difference between the proximal and distalpressure signals so as to maintain a pressure of fluid at a point ofentry into the peritoneum that corresponds to fixed head pressure,allowing a patient's peritoneum to be filled to a prescribed volumewithout exceeding a safe pressure limit, the prescribed volume includingthe peritoneum's full capacity. The supplying may be effective to limita pressure difference determined by a controller between the proximaland distal pressure signals. The supplying may be effective to limit apressure indicated by the distal pressure signal received by acontroller that controls a rate of pumping.

According to embodiments, the disclosed subject matter includes a methodof performing a dialysis treatment using a pump and a dialysate supplyline where the supply line has a proximal end into which peritonealdialysis fluid is supplied and from which spent dialysate withdrawn, anda distal end which is connected to a patient's peritoneal access. Themethod includes generating proximal and distal pressure signals usingpressure detectors located at both the proximal and distal ends,respectively, of the supply line, and reducing the flow rate or haltingthe flow of dialysis fluid when the difference between the proximal anddistal pressure signals rises above a threshold value. The method mayinclude generating an alarm that indicates a problem with the supplyline when the pressure difference between the proximal and distalpressure signals rises above the threshold value or when the differencebetween the proximal and distal pressure signals rises above a thresholdvalue, reducing the flow rate of the supplying. The method may include,when the difference between the proximal and distal pressure signalsrises above the threshold value, halting the supplying. The method mayinclude generating of an alarm indication responsively to a detection ofa high pressure drop in the supply line and outputting the an alarm andan indication of the type of the alarm on a digital display. The methodmay include generating of an alarm indication responsively to adetection of a high pressure drop in the supply line and recording adigital record of an error event in a non-volatile data store.

According to embodiments, the disclosed subject matter includes a methodof performing a dialysis treatment using a pump and a dialysate supplyline where the supply line has a proximal end into which peritonealdialysis fluid is supplied and from which spend dialysate is withdrawn,and a distal end which is connected to a patient's peritoneal access.The method includes generating proximal and distal pressure signalsusing pressure detectors located at both the proximal and distal ends,respectively, of the supply line and during a drain cycle in which spentdialysate is pumped from the patient, responsively to the proximal anddistal pressure signals, detecting a pressure difference between thedistal and proximal ends resulting from a change in dialysateproperties, and generating a signal indicating the change in dialysateproperties. The change in dialysate properties may include an increasein viscosity that causes an increase in pressure drop. The method mayinclude generating a display indicating a change in viscosity. Themethod may include recording in a non-volatile data store, an indicatorof a pathology event including an identifier of the dialysate propertiesand an identifier of a patient. The method may include transmitting amessage to a care provider service, the message indicating the pathologyevent.

According to embodiments, the disclosed subject matter includes acontroller programmed to implement a method according to any of theforegoing method claims.

According to embodiments, the disclosed subject matter includes acomputer readable medium having recorded thereon a computerimplementable procedure according to any of the foregoing method claims.

According to embodiments, the disclosed subject matter includes a systemconfigured to perform, automatically, any of the procedures of any ofthe foregoing method claims.

According to embodiments, the disclosed subject matter includes adisposable fluid circuit includes a peritoneal dialysis tubing setincluding connection tube with a connector for a peritoneal catheter ata distal end and a connector configured to connect to a peritonealcycler at a proximal end. The circuit includes a pressure pod at thedistal end, the pressure pod being of the type that has a flow chamberfor carrying a liquid and an air chamber separated from the flow chamberby a diaphragm and an air port in fluid communication with the airchamber. The flow chamber is connected in-line with a lumen of theconnection tube. The circuit includes a length of tubing running fromair-port along the length of the connection tube with a connector at theproximal end configured to connect to a pressure transducer. The fluidcircuit may be entirely of polymer, the lumen of the connection tube issealed at both ends and sterile. The distal end may have a peritonealcatheter with a lumen interconnected to the distal and with the lumen ofthe peritoneal catheter and the connection tube in flow communication.The fluid circuit may include a fluid container connected to theproximal end of the connection tube. The fluid circuit may include acontainer with at least one component of a medicament connected to theconnection tube lumen at the proximal end thereof. The fluid circuit mayinclude a first empty fluid container connected to the proximal end ofthe connection tube and a second filled fluid container with at leastone component of a medicament connected to the first empty fluidcontainer by at least one valve.

According to embodiments, the disclosed subject matter includes adisposable fluid circuit with a peritoneal dialysis tubing set includingconnection tube with a connector for a peritoneal catheter at a distalend and a connector configured to connect to a peritoneal cycler at aproximal end. The circuit may include a pressure transducer at thedistal end, the sensor having leads for connection to a driver circuit.The pressure transducer is in pressure communication with a lumen of theconnection tube. Leads may be attached to and run along the length ofthe connection tube with a connector on the leads at the proximal endand configured to connect to a driver circuit. The fluid circuit may besealed at both ends and sterile internally. The distal end may have aperitoneal catheter with a lumen interconnected to the distal and withthe lumen of the peritoneal catheter and the connection tube in flowcommunication. A fluid container may be connected to the proximal end ofthe connection tube. The fluid circuit may further include a containerwith at least one component of a medicament connected to the connectiontube lumen at the proximal end thereof. The fluid circuit may furtherinclude a first empty fluid container connected to the proximal end ofthe connection tube and a second filled fluid container with at leastone component of a medicament connected to the first empty fluidcontainer by at least one valve. The leads may be coaxial and/or RFshielded.

According to embodiments, the disclosed subject matter includes a fluidflow system for peritoneal dialysis with a pump. The pump has an inletand an outlet and is configured to pump fluid from the inlet to theoutlet. First flow paths are selectably connectable to the pump inlet,the first flow paths being connected respectively to respective sourcesof at least one concentrate and water, and to a dialysis fluid batchcontainer. Second flow paths are selectably connectable to the pumpoutlet, the second flow paths being connected respectively to thedialysis fluid batch container, a patient access line, and a drain. Acontroller may be included in the system and configured to operate thepump in a single direction. The first and second flow paths may includecontrol valves connected for control by a controller, the controllerbeing configured to operate the pump and the control valves to flow theat least one concentrate and water into the dialysis fluid batchcontainer, to mix the at least one concentrate. The controller may befurther configured to operate the pump and the control valves totransfer fluid from the dialysis fluid batch container to the patientaccess. The controller may be configured to operate the pump and thecontrol valves to transfer fluid from the patient access to the drain.The system may include a fluid property sensor in the second flow pathconnecting to the drain, wherein the controller is further configured tooperate the pump and the control valves to transfer fluid from thedialysis fluid batch container to the drain and to receive a signalindicating a property of the fluid. The at least one concentrate mayinclude an electrolyte and an osmotic agent. The at least oneconcentrate may include an electrolyte and osmotic agent.

According to embodiments, the disclosed subject matter includes aperitoneal dialysis system with a peritoneal fill line that includes aperitoneal catheter at a distal end thereof and connected to a source offluid at a proximal end thereof, the proximal end being opposite thedistal end. The system has a controller and a distal pressure sensor atthe distal end configured to apply a distal pressure signal to thecontroller as well as a proximal pressure sensor at the proximal endconfigured to apply a proximal pressure signal to the controller. Thecontroller is configured to detect a condition where a difference inpressures represented by the proximal and distal pressure signals exceeda predefined threshold and to generate a first output responsivelythereto. The controller may be further configured to access dataindicative of a target flow rate and to maintain a target flow rateresponsively to the data, and at least one of the proximal and distalpressure signals. The first output may be an alarm signal. Thecontroller may be configured to regulate a rate of flow of fluid in theperitoneal fill line and further configured such that the first outputincludes a command to change a flow rate of fluid in the peritoneal fillline. The controller may be configured to regulate a rate of flow offluid in the peritoneal fill line responsively to a difference inpressures represented by the proximal and distal pressure signals. Thecontroller may be configured to detect a pressure drop characteristicresponsive to a difference in pressures represented by the proximal anddistal pressure signals and responsive to the flow rate of fluid in theperitoneal fill line and generate a second output responsively to thepressure drop characteristic. The second output may include a UI outputon a user interface indicating a peritoneal fill line error condition.The second output may be generated when fluid is flowing from theproximal end to the distal end of the peritoneal fill line. The secondoutput may include a UI output on a user interface indicating a patienthealth condition. The second output may be generated when fluid isflowing from the distal end to the proximal end of the peritoneal fillline.

According to embodiments, the disclosed subject matter includes a fluidflow system for peritoneal dialysis with a cycler unit configured with apump actuator, a controller, and valve actuators. The controller isconfigured to operate the pump actuator and valve actuators to controlflow in first and second disposable circuits. The first disposable fluidcircuit includes valve portions configured to engage with the valveactuators, pump portions configured to engage with the pump actuator,and respective connections for water, at least one source ofconcentrate, one batch container, and a peritoneal fill line. The seconddisposable fluid circuit includes valve portions configured to engagewith the valve actuators, pump portions configured to engage with thepump actuator, and respective connections for at least one source ofdialysis fluid and a peritoneal fill line. The controller and cycler areconfigured to prepare a batch of peritoneal dialysis fluid using thefirst disposable fluid circuit and perform an automatic therapeutictreatment with the batch. The controller and cycler unit are furtherconfigured to use the second disposable fluid circuit to perform anautomatic therapeutic treatment with fluid from a source of dialysisfluid. The controller may be configured to operate the pump in a singledirection. The controller may be further configured to operate the pumpand the control valves to transfer fluid from the dialysis fluid batchcontainer to the peritoneal fill line. The controller may be furtherconfigured to operate the pump and the control valves to transfer fluidfrom the peritoneal fill line to a drain. A fluid property sensor may beprovided in the second flow path connecting to the drain, wherein thecontroller is further configured to operate the pump and the controlvalves to transfer fluid from the dialysis fluid batch container to thedrain and to receive a signal indicating a property of the fluid. Thesecond disposable fluid circuit respective connector(s) for peritonealdialysis fluid may include inline sterile filters.

While the present invention has been described in conjunction with anumber of embodiments, the invention is not to be limited to thedescription of the embodiments contained herein, but rather is definedby the claims appended hereto and their equivalents. It is furtherevident that many alternatives, modifications, and variations would beor are apparent to those of ordinary skill in the applicable arts.Accordingly, Applicant intends to embrace all such alternatives,modifications, equivalents, and variations that are within the spiritand scope of this invention.

In any of the foregoing embodiments, methods and systems and devices maybe implemented using well-known digital systems. It will be appreciatedthat the modules, processes, systems, and sections described and/orsuggested herein can be implemented in hardware, hardware programmed bysoftware, software instruction stored on a non-transitory computerreadable medium or a combination of the above. For example, a method forcontrolling the disclosed systems can be implemented, for example, usinga processor configured to execute a sequence of programmed instructionsstored on a non-transitory computer readable medium. For example, theprocessor can include, but not be limited to, a personal computer orworkstation or other such computing system that includes a processor,microprocessor, microcontroller device, or is comprised of control logicincluding integrated circuits such as, for example, an ApplicationSpecific Integrated Circuit (ASIC). The instructions can be compiledfrom source code instructions provided in accordance with a programminglanguage such as Java, C++, C#.net or the like. The instructions canalso comprise code and data objects provided in accordance with, forexample, the Visual Basic™ language, LabVIEW, or another structured orobject-oriented programming language. The sequence of programmedinstructions and data associated therewith can be stored in anon-transitory computer-readable medium such as a computer memory orstorage device which may be any suitable memory apparatus, such as, butnot limited to read-only memory (ROM), programmable read-only memory(PROM), electrically erasable programmable read-only memory (EEPROM),random-access memory (RAM), flash memory, disk drive and the like.

Furthermore, the modules, processes, systems, and sections can beimplemented as a single processor or as a distributed processor.Further, it should be appreciated that the steps mentioned above may beperformed on a single or distributed processor (single and/ormulti-core). Also, the processes, modules, and sub-modules described inthe various figures of and for embodiments above may be distributedacross multiple computers or systems or may be co-located in a singleprocessor or system. Exemplary structural embodiment alternativessuitable for implementing the modules, sections, systems, means, orprocesses described herein are provided below.

The modules, processors or systems described above can be implemented asa programmed general purpose computer, an electronic device programmedwith microcode, a hard-wired analog logic circuit, software stored on acomputer-readable medium or signal, an optical computing device, anetworked system of electronic and/or optical devices, a special purposecomputing device, an integrated circuit device, a semiconductor chip,and a software module or object stored on a computer-readable medium orsignal, for example.

Embodiments of the method and system (or their sub-components ormodules), may be implemented on a general-purpose computer, aspecial-purpose computer, a programmed microprocessor or microcontrollerand peripheral integrated circuit element, an ASIC or other integratedcircuit, a digital signal processor, a hardwired electronic or logiccircuit such as a discrete element circuit, a programmed logic circuitsuch as a programmable logic device (PLD), programmable logic array(PLA), field-programmable gate array (FPGA), programmable array logic(PAL) device, or the like. In general, any process capable ofimplementing the functions or steps described herein can be used toimplement embodiments of the method, system, or a computer programproduct (software program stored on a non-transitory computer readablemedium).

Furthermore, embodiments of the disclosed method, system, and computerprogram product may be readily implemented, fully or partially, insoftware using, for example, object or object-oriented softwaredevelopment environments that provide portable source code that can beused on a variety of computer platforms. Alternatively, embodiments ofthe disclosed method, system, and computer program product can beimplemented partially or fully in hardware using, for example, standardlogic circuits or a very-large-scale integration (VLSI) design. Otherhardware or software can be used to implement embodiments depending onthe speed and/or efficiency requirements of the systems, the particularfunction, and/or particular software or hardware system, microprocessor,or microcomputer being utilized. Embodiments of the method, system, andcomputer program product can be implemented in hardware and/or softwareusing any known or later developed systems or structures, devices and/orsoftware by those of ordinary skill in the applicable art from thefunction description provided herein and with a general basic knowledgeof control systems and/or computer programming arts.

Moreover, embodiments of the disclosed method, system, and computerprogram product can be implemented in software executed on a programmedgeneral purpose computer, a special purpose computer, a microprocessor,or the like.

It is, thus, apparent that there is provided, in accordance with thepresent disclosure, peritoneal dialysis devices, methods and systems.Many alternatives, modifications, and variations are enabled by thepresent disclosure. Features of the disclosed embodiments can becombined, rearranged, omitted, etc., within the scope of the inventionto produce additional embodiments. Furthermore, certain features maysometimes be used to advantage without a corresponding use of otherfeatures. Accordingly, Applicants intend to embrace all suchalternatives, modifications, equivalents, and variations that are withinthe spirit and scope of the present invention.

1. A method of performing a peritoneal dialysis treatment, comprising:connecting a disposable unit to a source of water, said disposable unitincluding at least a first container holding a sterile concentratecontaining an osmotic agent, a second container holding a sterileconcentrate containing electrolytes, an empty sterile mixing container,and a tubing set with a pre-attached peritoneal fill/drain line;receiving a prescription command by a controller, indicating at leastthe fill volume and desired final concentration of the osmotic agent tobe used for a current fill cycle under said treatment; using thecontroller, pumping a quantity of the concentrated osmotic agent that isat least sufficient to achieve the desired final concentration into themixing container; mixing the contents of the mixing container; furtherdiluting or further adding concentrated osmotic agent to the mixingcontainer; and flowing fluid from the mixing container to a patient. 2.The method of claim 1, further comprising: prior to the pumping aquantity of the concentrated osmotic agent, responsively to theprescription command, using the controller, pumping a volume of waterfrom the source of water into the mixing container.
 3. The method ofclaim 2, further comprising: after the mixing, detecting theconcentration of osmotic agent in the mixing container.
 4. The method ofclaim 3, wherein said first container holds a sterile concentratecontaining both an osmotic agent and a predefined mixture containingelectrolytes, said mixture serving as a marker for the purpose ofestablishing a conductivity versus concentration characteristic that ismonotonic within a range suitable for closed-loop control.
 5. The methodof claim 4, further comprising: pumping into the mixing container aquantity of the concentrated electrolytes from said second containerthat, in combination with the selected quantity of concentrate pumpedfrom said first container, will result, upon further dilution, in thedesired final dialysis fluid formulation; mixing the contents of themixing container; detecting the total concentration of electrolytes inthe mixing container; further diluting or further adding concentratedelectrolytes to the mixing container responsively to a result of thedetecting; and flowing fluid from the mixing container to a patient. 6.The method of claim 5, wherein the electrolyte marker is the samespecies as the electrolyte concentrate held in said second container. 7.The method of claim 6, wherein the detecting the concentration ofosmotic agent includes detecting the concentration of the electrolytemarker using a conductivity sensor, whereby the concentration of theosmotic agent is inferred from an attending concentration ofelectrolyte.
 8. The method of claim 7, wherein the electrolyte markerand osmotic agent have been proportioned such that only concentrate fromsaid first container is needed when the prescription command calls forthe maximum desired concentration.
 9. The method of claim 8, wherein thedisposable unit also includes a third container holding a buffer. 10.The method of claim 9, wherein the pH of the concentrated osmotic agentheld in said first container is less than 4.0 and the pH of theconcentrates held in said second and/or third containers is such thatthe pH of the final formulation will be in the range of 6.0 to 8.0. 11.The method of claim 10, wherein the osmotic agent is, or includes,glucose.
 12. The method of claim 11, wherein the osmotic agent has beenprepared via sterile filtration.
 13. The method of claim 12, whereinsaid disposable unit also includes a sterilizing-grade filter.
 14. Themethod of claim 13, further comprising: passing water from said sourcethrough said sterilizing-grade filter prior to flowing into said mixingcontainer, and; confirming the integrity of said filter prior tosupplying fluid to a patient.
 15. The method of claim 14, furthercomprising: passing the contents of said first and second containers,through said sterilizing-grade filter prior to flowing into said mixingcontainer, and; confirming the integrity of said filter prior tosupplying fluid to a patient.
 16. The method of claim 15, wherein saidvolume of water is initially less than 110%, and preferably less than100%, of the prescribed fill volume.
 17. The method of claim 16, whereinsaid dialysis treatment includes multiple fill cycles, and said fillvolumes and desired final concentrations of the osmotic agent may varyfrom cycle to cycle.
 18. The method of claim 8, wherein the maximumdesired concentration is 4.25% for dextrose.